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Iovanna, Juan

https://orcid.org/0000-0003-1822-2237

Mayo Clinic

Centre National de la Recherche Scientifique

Citations 19

Mutant KRAS Heterogeneity Shapes Nuclear Architecture During Pancreatic Cancer Initiation
Pollin, Gareth , Leverence, Elise, Assuncao, Thiago M. de , Iovanna, Juan, Hong, Johnny C. , Zimmermann, Michael T. , Urrutia, Raúl , Lomberk, Gwen , Mathison, Angela J , Zimmermann, Michael T , Urrutia, Raul , Lomberk, Gwen L , Mathison, Angela , Iovanna, Juan

Epigenomes | March 10, 2026 | Volume: 10 | Issue: 1 | Pages: 19

10.3390/epigenomes10010019 Get It

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) arises predominantly from activating KRAS mutations, yet individual genetic variants differ markedly in signaling output and clinical impact. G12D, the most prevalent variant, strongly drives oncogenic programs, whereas G12R signals less efficiently through the AKT and ERK pathways and is associated with longer patient survival than G12D-driven PDAC. Methods: To elucidate how these differences influence early cellular transformation, we expressed a panel of KRAS mutants in non-cancerous pancreatic ductal epithelial cells as a model of early PDAC initiation and profiled transcriptional and phospho-proteomic responses. We next examined whether epigenetic differences translate into mutation-specific changes in nuclear organization using quantitative imaging of G12D- and G12R-expressing nuclei at 24 and 48 h. Results: Each variant established a unique regulatory program enriched for chromatin remodelers, histone modifiers, and nuclear structural factors, indicating that variant-specific KRAS signaling rapidly develops divergent epigenetic states. Integrated transcriptomic and phospho-proteomic analyses identified G12D and G12R as the most divergent variants. G12D induced pronounced nuclear remodeling, including increased nuclear size, irregular morphology, and reorganization of the nucleolus and spliceosome, consistent with extensive chromatin and transcriptional reprogramming. In contrast, G12R elicited a weaker response, with minimal or delayed structural changes. Conclusions: Together, these findings demonstrate that KRAS mutational context in pancreatic ductal epithelial cells shapes early transcriptional reprogramming that actively remodels nuclear architecture and nuclear sub-compartments. This work establishes nuclear structural remodeling as a structural state of KRAS-driven epigenetic dysregulation during PDAC initiation.
Oncogenic stress response mechanisms as new therapeutic targets in cancer treatment: A review
Iovanna, Juan , Estarás, Matías , Grasso, Daniel , Zapico, Martin E. Fernández, Santofimia‐Castaño, Patricia , Fernández Zapico, Martin E, Iovanna, Juan , Santofimia-Castaño, Patricia , Neira, José L.

Medicine | June 18, 2025 | Volume: 104 | Issue: 24 | Pages: e42857

10.1097/md.0000000000042857 Get It

Activation of oncogenes, such as through mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS), triggers profound disruptions in cellular homeostasis that set off a cascade of stress responses. These responses enable cells to cope with the array of challenges encountered during tumorigenesis by activating defense mechanisms that promote adaptation and survival. Key components of this oncogenic stress response include heat shock proteins, the ubiquitin-proteasome system, autophagy, nuclear factor erythroid 2-related factor 2–antioxidant response element signaling, DNA damage response proteins, p53, redox-regulating proteins, and stress granules. This review concentrates on KRAS-driven oncogenic transformation, as KRAS mutations are among the most common in human cancers, accounting for over 90% of pancreatic ductal adenocarcinoma cases, around 30% of lung cancers, and approximately 50% of colorectal cancers. We examine the intricate molecular interplay between oncogenic stress and the associated cellular defense mechanisms, emphasizing the key molecular events that follow KRAS activation. Importantly, the very pathways that allow cancer cells to adapt to oncogenic stress also offer novel therapeutic opportunities. By selectively targeting pivotal regulators within these stress response pathways, we can potentially disrupt the survival mechanisms of cancer cells. This strategy not only promises to enhance the effectiveness of existing treatments but also paves the way for the development of innovative therapies designed to combat tumor progression. In essence, exploiting oncogenic stress responses represents an original and promising therapeutic approach in the fight against cancer.
Nuclear Galectin-1 promotes KRAS -dependent activation of pancreatic cancer stellate cells
Vinaixa, Judith , Gibert, Joan , Manero‐Rupérez, Noemí, Santofimia‐Castaño, Patricia , Baudou, Federico G. , Vera, Renzo E., Pease, David R. , Iglesias, Mar , Sen, Sandhya , Almada, Luciana L. , Marks, David L. , Fernández-Zapico, Martín E. , Navarro, Pilar , Santofimia-Castaño, Patricia , Iovanna, Juan , Rabinovich, Gabriel A , Navarro, Pilar , Martínez‐Bosch, Neus , Wang, Xiyin , Moreno, Mireia, Iovanna, Juan , Navarro, Pilar

Proceedings of the National Academy of Sciences | April 2, 2025 | Volume: 122 | Issue: 14 | Pages: No page available

10.1073/pnas.2424051122 Get It

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, primarily due to its complex tumor microenvironment (TME), which drives both disease progression and therapy resistance. Understanding the molecular mechanisms governing TME dynamics is essential for developing new treatment strategies for this devastating disease. In this study, we uncover an oncogenic role for Galectin-1 (Gal1), a glycan-binding protein abundantly expressed by activated pancreatic stellate cells (PSCs), a key component of the PDAC TME that orchestrates tumor progression. Our findings reveal that Gal1 expression is elevated in the nucleus of human PSCs in both tissue samples and cultured cell lines. Using chromatin immunoprecipitation followed by sequencing analysis (ChIP-seq), we identify Gal1 occupancy at the promoters of several cancer-associated genes, including KRAS , a pivotal oncogene involved in PDAC pathogenesis. We demonstrate that Gal1 binds to the KRAS promoter, sustaining KRAS expression in PSCs, which, in turn, maintains PSC activation and promotes the secretion of protumorigenic cytokines. Mechanistically, Gal1 is required to preserve histone H3 lysine 4 monomethylation levels and to recruit the histone methyltransferase MLL1 to target promoters. Collectively, our findings define a nuclear function of Gal1 in modulating the transcriptional landscape of cancer-associated genes in PSCs within the PDAC TME, mediated through an epigenetic mechanism. These insights enhance our understanding of PDAC pathology and open potential avenues for therapeutic interventions targeting intracellular Gal1.
Writers and readers of H3K9me2 form distinct protein networks during the cell cycle that include candidates for H3K9 mimicry
Pollin, Gareth , Assuncao, Thiago M. de , Jorge, Salomão Dória , Chi, Young‐In , Charlesworth, M. Cristine , Lomberk, Gwen , Lomberk, Gwen L , Charlesworth, M. Cristine , Madden, Benjamin J. , Iovanna, Juan , Zimmermann, Michael T. , Urrutia, Raúl

Bioscience Reports | October 2, 2023 | Volume: 43 | Issue: 10 | Pages: No page available

10.1042/bsr20231093 Get It

Abstract Histone H3 lysine 9 methylation (H3K9me), which is written by the Euchromatic Histone Lysine Methyltransferases EHMT1 and EHMT2 and read by the heterochromatin protein 1 (HP1) chromobox (CBX) protein family, is dysregulated in many types of cancers. Approaches to inhibit regulators of this pathway are currently being evaluated for therapeutic purposes. Thus, knowledge of the complexes supporting the function of these writers and readers during the process of cell proliferation is critical for our understanding of their role in carcinogenesis. Here, we immunopurified each of these proteins and used mass spectrometry to define their associated non-histone proteins, individually and at two different phases of the cell cycle, namely G1/S and G2/M. Our findings identify novel binding proteins for these writers and readers, as well as corroborate known interactors, to show the formation of distinct protein complex networks in a cell cycle phase-specific manner. Furthermore, there is an organizational switch between cell cycle phases for interactions among specific writer–reader pairs. Through a multi-tiered bioinformatics-based approach, we reveal that many interacting proteins exhibit histone mimicry, based on an H3K9-like linear motif. Gene ontology analyses, pathway enrichment, and network reconstruction inferred that these comprehensive EHMT and CBX-associated interacting protein networks participate in various functions, including transcription, DNA repair, splicing, and membrane disassembly. Combined, our data reveals novel complexes that provide insight into key functions of cell cycle-associated epigenomic processes that are highly relevant for better understanding these chromatin-modifying proteins during cell cycle and carcinogenesis.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
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Tariq, Ahumada-Castro, Ulises , Aits, Sonja , Aizawa, Shu, Akkoç, Yunus , Akoumianaki, Tonia, Akpinar, Hafize Aysin , Al‐Abd, Ahmed M. , Al-Akra, Lina, Gharaibeh, Abeer , Alaoui‐Jamali, Moulay A. , Alberti, Simon , Alessandri, Cristiano , Alonso, Alicia , Altan‐Bonnet, Nihal , Álvarez, Élida, Alves, Sara , Costa, Cristine Alvès da , Alzaharna, Mazen M. , Amadio, Marialaura , Amantini, Consuelo , Amaral, Cristina , Ambrosio, Susanna , Amer, Amal O. , Ammanathan, Veena , An, Zhenyi, Andrabi, Shaida A. , Andres, Allen M. , Ann, David K. , Anozie, Uche C. , Ansari, Mohammad Y. , Antas, Pedro , Antebi, Adam , Antón, Zuriñe , Anwar, Tahira , Apétoh, Lionel , Araki, Toshiyuki , Araki, Yasuhiro , Araya, Jun , Arévalo, María‐Ángeles , Argüelles, Sandro , Arias, Esperanza , Arikkath, Jyothi , Ariosa, Aileen, Aroca, Ángeles , Arroyo, Daniela S., Arsov, Ivica, Artero, Rubén , Asaro, Dalia Maria Lucia, Ashur‐Fabian, Osnat , Atanasov, Atanas G. , Au, Alicia K. , Auberger, Patrick , Auner, Holger W. , Aurelian, Laure , Avagliano, Laura , Ávalos, Yenniffer , Aveleira, Célia A. , Aydın, Yücel , Ayyadevara, Srinivas , Azzopardi, Maria , Baba, Misuzu, Backer, Jonathan , Bae, Soo Han , Baehrecke, Eric H. , Bagetta, Giacinto , Bagniewska‐Zadworna, Agnieszka , Bai, Hua , Bai, Xiyuan , Bairagi, Nandadulal , Baksi, Shounak , Balbi, Teresa , Ballester, María , Balazadeh, Salma , Balzan, Rena , Bandopadhyay, Rina , Banerjee, Sulagna , Bánréti, Ágnes , Baracca, Alessandra , Barbati, Cristiana , Bargiela, Ariadna , Barilà, Daniela , Barlow, Peter G. , Barmada, Sami J. , Barreiro, Esther , Bártek, Jiří , Bartel, Bonnie , Bartolomé, Alberto , Barve, Gaurav , Bassham, Diane C. , Baulieu, E.E. , Baumgarner, Bradley L. , Bayry, Jagadeesh , Beale, Rupert , Beau, Isabelle , Beaumatin, Florian , Bechara, Luiz Roberto Grassmann , Beck, George R. , Beers, Michael F. , Begun, Jakob , Behrends, Christian , Bejarano, Eloy , Bel, Shai , Belaïd, Amine , Belgareh‐Touzé, Naïma, Bellarosa, Cristina , Belleudi, Francesca , Belló-Pérez, Melissa , Beltran, Jackeline Soares de Oliveira , Beltran, Sebastián, Benbrook, Doris M. , Bendorius, Mykolas , Benítez, Bruno A. , Benito‐Cuesta, Irene , Bensalem, Julien , Berchtold, Martin W. , Berezowska, Sabina , Bergamaschi, Daniele , Berliocchi, Laura , Berlioz‐Torrent, Clarisse , Bernard, Amélie , Besirli, Cagri G. , Besteiro, Sébastien , Betin, Virginie M.S., Beyaert, Rudi , Bezbradica, Jelena S. , Bhaskar, Kiran , Bhatia‐Kiššová, Ingrid, Bhattacharya, Sujoy , Bhuiyan, Md. 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Brent, Carvalho, Andreia Neves , Casanova, Magali , Casas, Josefina , Cassioli, Chiara , Castillo, Karen , Castillo‐Lluva, Sonia , Castoldi, Francesca , Castori, Marco , Castro, Ariel F. , Castro‐Hernández, Javier , Cavadas, Cláudia , Cavaliere, Federica, Cavallini, Gabriella , Cavinato, Maria , Rica, Paula Cebollada , Cechowska‐Pasko, Marzanna , Cerqueira, João , Cerutti, Janete M. , Çetintaş, Vildan Bozok , Cetrullo, Silvia , Chagin, Andrei S. , Chai, Chee‐Yin , Chakrabarti, Gopal , Chakraborty, Tapas , Chakraborty, Trinad , Chami, Mounia , Chamilos, Georgios , Chan, David W. , Chan, Edmond Y. 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De , Palma, Clara De , Virgilio, Claudio De , Zio, Daniela De , Decuypere, Jean-Paul , Deehan, Mark , Deflorian, Gianluca , Dehay, Benjamin , Delaney, Joe R. , Delorme‐Axford, Elizabeth , Demers, Nicholas D. , Deng, Hongbin , Dengjel, Jörn , Dent, Paul, DePamphilis, Melvin L., Descoteaux, Albert , Devis, Laura , Devkota, Sushil , Devuyst, Olivier , Dewson, Grant , Dharmasivam, Mahendiran , Domenico, Fabio Di , Fazio, Pietro Di , Fonzo, Alessio Di , Guardo, Giovanni Di , Guglielmo, Gianni M. Di , Leo, Luca Di , Malta, Chiara Di , Nardo, Alessia Di, Rienzo, Martina Di , Diao, Jiajie , Diaz-Araya, Guillermo, Díaz‐Laviada, Inés , Dickinson, Jared M. , Diederich, Marc , Dieudé, Mélanie , Ding, Shiping , Ding, Wen-Xing, Dinić, Jelena , Dinić, Miroslav , Dinkova‐Kostova, Albena T. , Distler, Jörg H. W. , Đokić, Jelena , Emre, Serap , Dong, Xiaonan , Dong, Zhiwu , Dorn, Gerald W. , Dou, Juan, Dowaidar, Moataz , Drucker, Liat , Du, Ailian , Du, Guangwei , Du, Hai‐Ning , Toit, André du , Duan, Shao-Bin , Duan, Xiaoqiong , Duarte, Sónia , Dupont, Nicolas , Durán, Raúl V. , Dyshlovoy, Sergey A. , Ebrahimi‐Fakhari, Darius , Eckhart, Leopold , Edelstein, Charles L. , Efferth, Thomas , Eid, Nabil , Eisenberg, Tobias , Eissa, N. Tony, Ejarque, Miriam , Andaloussi, Abdeljabar El, El‐Hage, Nazira , Eleuteri, Anna Maria , El‐Shafey, Eman S. , Elgendy, Mohamed , Elizalde, María Mercedes , Elsässer, Hans‐Peter , Elsherbiny, Eslam S. , Emre, N. C. Tolga , Eng, Christina H. , Engedal, Nikolai , Engelsen, Agnete S. T. , Enserink, Jorrit M. , Escalante, Ricardo , Esclatine, Audrey , Eskelinen, Eeva‐Liisa , Espert, Lucile , Eusebio, Makandjou-Ola , Facchiano, Antonio , Facchiano, Francesco , Fadeel, Bengt , Fader, Claudio M., Faesen, Alex C. , Fairlie, W. Douglas , Falcó, Alberto , Fan, Daping , Fan, Jie , Fang, Evandro Fei , Fang, Yanshan , Fang, Yognqi, Farfel‐Becker, Tamar, Faure, Mathias , Fazeli, Gholamreza , Fedele, Anthony O., Feldman, Arthur M. , Feng, Jiachun , Feng, Lifeng , Feng, Wei , Araujo, Thaís Fenz , Ferguson, Thomas A., Fernández, Álvaro F. , Fernández‐Veledo, Sonia , Fernie, Alisdair R. , Ferrante, Anthony W. , Ferraresi, Alessandra , Ferrari, M , Ferreira, Julio Cesar Batista , Ferro‐Novick, Susan , Figueras, António , Filadi, Riccardo , Filigheddu, Nicoletta , Fimia, Gian María , Finetti, Francesca , Finkbeiner, Steven , Fisher, Edward A. , Fisher, Paul B. , Fliesler, Steven J. , Flo, Trude Helen , Florance, Ida , Florey, Oliver , Florio, Tullio , Fodor, Erika , Forlino, Antonella , Fortini, Paola , Fracassi, Anna , Franconi, Flavia , Frankel, Lisa B. , Fröhlich, Leopold F. , Fuentes, José M. , Fujiki, Yukio , Fulda, Simone , Furuya, Norihiko , Gack, Michaela U. , Gaffke, Lidia , Galadari, Sehamuddin , Galasso, Alessia , Galindo, Marı́a F. , Kankanamalage, Sachith Gallolu , Galluzzi, Lorenzo, Galy, Vincent , Gammoh, Noor , Ganley, Ian G. , Gao, Feng , Gao, Minghui , Gao, Ping , Gao, Wentao , Gao, Xiaobo , Garcerá, Ana , Garcia, María Noé , García, Verónica , Portillo, Francisco Garcı́a-del , García‐Escudero, Vega , García‐García, Aracely , García‐Macía, Marina , García‐Moreno, Diana , García‐Ruiz, Carmen , García‐Sanz, Patricia , Garg, Abhishek D. , Garofalo, Tina , Gassen, Nils C. , Gatica, Damián , Geiss‐Friedlander, Ruth , Genschik, Pascal , Gerbino, Valeria , Gerhardt, Christoph , Germain, Kyla , Germain, Marc , Afshar, Elham Ghasemipour, Ghavami, Saeid , Ghosh, Manosij , Giamas, Georgios , Giatromanolaki, Alexandra , Gibson, Gary E. , Ginet, Vanessa, Girardin, Stephen E. , Giridharan, Mridhula, Giuliano, Sandy , Giulivi, Cecilia , Giuriato, Sylvie , Giustiniani, Julien , Gluschko, Alexander , Goder, Veit , Goginashvili, Alexander , Gołąb, Jakub , Golebiewska, Anna , Gomes, Luciana Rodrigues, Gomez, Rodrigo Enrique, Gómez‐Sánchez, Rubén , Gómez‐Sintes, Raquel , Gong, Qingqiu , González‐Gallego, Javier , González‐Polo, Rosa A. , González‐Reyes, José A. , González-Rodríguez, Patricia , Goping, Ing Swie , Gorbunov, Nikolai V., Görgülü, Kıvanç , Gorojod, Roxana Mayra , Gorski, Sharon M. , Gotor, Cecilia , Gözüaçık, Devrim , Graef, Martin , Gräler, Markus H. , Granatiero, Veronica, Grasso, Daniel , Gray, Joshua P. , Greenhough, Alexander , Gregory, Stephen L. , Griffin, Edward F., Gros, Frédéric , Grose, Charles , Gross, Angelina S. , Грубер, Флориан , Grumati, Paolo , Gu, Xueyan , Guan, Jun‐Lin , Guardia, Carlos M. , Guda, Kishore , Guerra, Flora , Guerri, Consuelo , Guha, Prasun , Guillén, Carlos , Gujar, Shashi , Gukovskaya, Anna S. , Gukovsky, Ilya , Gunst, Jan , Günther, Andreas , Guo, Chuanyong , Guo, Chun , Guo, Hongqing , Guo, Ming , Gupta, Pawan , Gupta, Swapnil , Gupta, Veer Bala , Gupta, Vivek , Gutterman, David D. , H.B., Ranjitha, Haber, James E. , Hać, Aleksandra , Haidar, Mansour , Halldén, Gunnel , Hamacher‐Brady, Anne , Hamasaki, Maho , Hansen, Malene , Hao, Zijian, Harada, Masaru , Harhaji‐Trajkovic, Ljubica , Hariharan, Nirmala , Haspel, Jeffrey A. , Haucke, Volker , Hawkins, Wayne D. , Haynes, Cole M. , Hays, Thomas S. , He, Congcong , He, Qin , He, Rong‐Rong , He, You‐Wen , Heakal, Yasser, Heberle, Alexander Martin , Hejtmancik, J. Fielding , Henkel, Vanessa, Herb, Marc , Herman-Antosiewicz, Anna , Hernández, Agustín , Hernández, Carlos , Hernández-Díaz, Sergio , Hernández–Gea, Virginia , Herpin, Amaury , Herreros, Judit , Hervás, Javier H. , Hesselson, Daniel , Hetz, Claudio , Higuchi, Yujiro , Hilfiker, Sabine , Hill, Joseph A., Ho, Emmanuel A. , Ho, Idy H. T. , Ho, Philip Wing‐Lok , Ho, Shu‐Leong , Ho, Wan Yun, Hoet, Peter , Hofius, Daniel , Höhn, Annika , Hong, Yi-Ren Hong Chang-Won, Hooper, Lora V. , Hsin, I‐Lun , Hu, Bing , Hu, Dong , Hu, Wei , Hu, Zhuowei , Hua, Jinlian, Huan, Chongmin , Huang, Chuanshu , Huang, Chunling , Huang, Haishan , Huang, Michael , Huang, Shan , Huang, Tianzhi , Huang, Xing , Huang, Yuxiang , Hubert, Virginie , Hübner, Christian A. , Hughes, Stephanie M. , Hughes, William E. , Hummer, Gerhard , Hurley, James H. , Hussain, Sabah N. A. , Hussain, Salik , Hutabarat, Martina , Hwang, Hui-Yun, Ieni, Antonio , Ikeda, Fumiyo , Imagawa, Yusuke , Imbriano, Carol , Imoto, Masaya , Inman, Denise M. , Inoki, Ken , Iozzo, Renato V. , Iribarren, Pablo , Ishaq, Mohd , Ishimwe, Nestor , Ismail, Nahed , Issazadeh‐Navikas, Shohreh , Itakura, Eisuke , Ito, Daisuke , Ivankovic, Davor , Ivanova, Saška , Iyer, Anand Krishnan V. , Izquierdo, José M. , Jacobo‐Herrera, Nadia , Jacquin, Élise , Jadiya, Pooja , Jaeschke, Hartmut , Jagannath, Chinnaswamy, Jakobsson, Johan , Janji, Bassam , Jansen‐Dürr, Pidder , Jansson, Patric J. , Januszewski, Sławomir, Jeltsch‐David, Hélène , Jenny, Andreas , Jensen, Thomas E. , Jessen, Niels , Jia, Lijun , Jia, Rui , Jiang, Qing , Jiang, Richeng , Jiang, Teng , Jiang, Xuejun , Jiang, Yu , Jiménez-Sánchez, María , Jin, Fengyan , Jin, Li , Jin, Luqi, Jin, Si , Joffre, Carine , Johnston, Simon A. , Jokitalo, Eija , Juárez, Esmeralda , Juhász, Gábor , Jun, Youngsoo , Jung, Chang Hwa , Jung, Sung‐Chul , Jungbluth, Heinz , Jungverdorben, Johannes , Just, Steffen , Kaasik, Allen , Kaganovich, Daniel , Kain, Renate , Kajimura, Shingo , Kalamvoki, Maria , Kalia, Manjula , Kalinowski, Danuta S. , Kaludercic, Nina , Kalvari, Ioanna , Kamińska, Joanna , Kanamori, Hiromitsu , Kang, Chanhee , Kang, Rui , Kang, Sang Sun , Kaniyappan, Senthilvelrajan , Kanki, Tomotake , Kanneganti, Thirumala‐Devi , Kanthasamy, Arthi , Kantorow, Marc , Kapuy, Orsolya , Karim, Md. Razaul , Kato, Masaru , Kauppinen, Anu , Kaushal, Gur P. , Kawasaki, Kiyoshi, Kazan, Kemal , Keber, Ursula , Keller, Kate E. , Kenific, Candia M. , Kepp, Oliver , Kern, Andreas , Keulers, Tom G. , Khalfin, Boris , Khalil, Hany , Khan, Shahid Y. , Khandelwal, Vinoth Kumar Megraj, Khandia, Rekha , Kho, Widuri , Khobrekar, Noopur V. , Khuansuwan, Sataree , Khundadze, Mukhran , Killackey, Samuel A. , Kim, Dasol , Kim, Deok Ryong, Kim, Do‐Hyung , Kim, Dong‐Eun , Kim, Eun‐Kyoung , Kim, Hak-Rim, Kim, Hee-Sik , Kim, Hyung-Ryong, Kim, Jeong Hun , Kim, Joungmok , Kim, Seong‐Jun , Kimball, Scot R., Kimchi, Adi , Kimmelman, Alec , Kimura, Tomonori , King, Matthew, Kinsey, Conan G. , Kirshenbaum, Lorrie A. , Kishi, Shuji , Kitamoto, Katsuhiko , Kitaoka, Yasushi , Kitazato, Kaio, Kitsis, Richard N. , Kjærulff, Ole , Klein, Peter S. , Klopstock, Thomas , Klucken, Jochen , Knævelsrud, Helene , Ko, Fred , Kobayashi, Satoru, Koch, Ina , Koch, Jan Christoph , Kögel, Donat , Koh, Young Ho , Kocatürk, Nur Mehpare , Komatsu, Masaaki, König, Jeannette , Kono, Toru, Korkmaz, Gözde , Korsnes, Mónica Suárez , Koskela, Ali , Kota, Janaiah , Kotake, Yaichiro , Kotler, Monica L., Kou, Yanjun , Koukourakis, Michael I., Koustas, Evangelos , Kovács, Tibor , Kovács, Tibor, Kraft, Claudine , Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna , Kretz‐Remy, Carole , Kroemer, Guido, Kuenen, Sabine , Kuerschner, Lars , Kukar, Thomas , Kumar, Ajay , Kumar, Deepak, Kumar, Dhiraj, Kumar, Sharad , Kume, Shinji , Kumsta, Caroline , Kundu, Chanakya Nath , Kundu, Mondira, Kunnumakkara, Ajaikumar B. , Kutlu, Özlem , Kwak, SeongAe , Kwon, Yong Tae , Spada, Albert La, Labonté, Patrick , Ladoire, Sylvain , Laface, Ilaria, Lafont, Frank , Lagace, Diane C. , Lahiri, Vikramjit , Lai, Zhibing, Laird, Angela S. , Lakkaraju, Aparna , Lan, Sheng‐Hui , Landajuela, Ane , Lane, Darius J.R. , Lange, Carsten , Langer, Rupert , Lapaquette, Pierre, Laporte, Jocelyn , Lastres-Becker, Isabel, Lau, Wilson Chun Yu , Laurie, Gordon W. , Le, Weidong, Stunff, Hervé Le , Leary, Alexandre Y , Lebrun, Jean-Jacques, Leck, Lionel , Lee, Changwook , Lee, Chung‐Pei , Lee, Da-Hye , Lee, Edward B., Lee, Erinna F. , Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu , Lee, Jason S. , Lee, Jin-A, Lee, Joo‐Yong , Lee, Michael , Lee, Min Goo , Lee, Min Jae, Lee, Myung‐Shik , Lee, Sangyoon , Lee, Stella Y. , Lee, Sung, Lee, Won Hee , Lee, Yong‐ho , Lee, Youngil , Lei, Yu L., Lei, Yuchen , Leikin, Sergey , Lemus, Leticia , Leng, Shuilong, Lenoir, Olivia , Lenz, Guido , Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda , Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth , Leung, Chi-Ting, Leung, Po Sing , Leventhal, Jeremy S. , Levine, Beth, Lewis, Patrick A. , Ley, Klaus , Li, Bin , Li, Da‐Qiang , Li, Jian‐Ming , Li, Jiong , Li, Liwu , Li, Mei , Li, Ming , Li, Mingchuan , Li, Pin‐Lan, Li, Ming‐Qing , Li, Qing , Li, Sheng , Li, Wei , Li, Wenming , Li, Xue , Li, Yi-Ping, Li, Yuan , Li, Zhiqiang, Li, Zhiyong , Li, Zhiyuan , Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng , Liang, Yongheng, Liang, YongTian , Liao, Guanghong , Liao, Lujian , Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl P.Y. , Lim, Hyunjung J., Lima, Thania Rios Rossi , Limana, Federica , Lin, Chao , Lin, Chih-Wen, Lin, Dar‐Shong , Lin, Fu‐Cheng , Lin, Jiandie D. , Lin, Kurt M., Lin, Kwang‐Huei , Lin, Qiong, Lin, Shaofeng , Lin, Su-Ju, Lin, Wenyu , Lin, Yao‐Xin , Lin, Yee‐Shin, Linden, Rafael, Lindner, Paula , Lipinski, Marta M. , Lipovšek, Saška, Lisiak, Natalia , Liton, Paloma B. , Liu, Chao , Liu, Ching‐Hsuan , Liu, Fang , Liu, Hua-feng , Liu, Huifang , Liu, Jia , Liu, Jing , Liu, Leyuan, Liu, Wei , Liu, Wende , Liu, Xiao-Hong, Liu, Xu , Liu, Yanfen , Liu, Yang, Liu, Yang, Liu, Yueyang , Liu, Yule , Livingston, J. 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H. , Ma, Ning-Fang, Ma, Quanhong , Ma, Xinliang , Ma, Yueyun , Ma, Zhenyi , MacDougald, Ormond A. , MacIntosh, Gustavo C. , Macleod, Kay F. , Maday, Sandra , Madeo, Frank , Madesh, Muniswamy , Madl, Tobias , Madrigal‐Matute, Julio , Maeda, Akiko, Maejima, Yasuhiro , Magariños, Marta , Mahavadi, Poornima , Maiani, Emiliano , Maiese, Kenneth , Maiti, Panchanan , Maiuri, Maria Chiara , Major, Michael Ben, Makareeva, Elena , Malik, Fayaz , Mallilankaraman, Karthik , Maloyan, Alina , Mammadova, Najiba, Man, Gene Chi Wai , Manai, Federico , Mancias, Joseph D. , Mandelkow, Eva‐Maria , Manfredi, Angelo A. , Manshian, Bella B. , Manzano, Raquel , Marchese, Chiara , Marchetti, Sandrine , Marcucci, F, Mardente, Stefania , Mareninova, Olga A. , Mari, Muriel , Marinelli, Sara , Mariño, Guillermo , Mariotto, Sofia , Martin, Alexandre , Martin, Katie R. , Martin, Sara L. , Martín‐Segura, Adrián , Martin-Burriel, Inmaculada, Martín-Rincón, Marcos , Martín‐Sanz, Paloma , Martinez, Aitor , Martı́nez, Ana , Martinez-Lopez, Nuria, Martínez‐Vicente, Marta , Martins, Daniel Oliveira , Martins, Joilson O. , Martins, Waleska K. , Martins-Marques, Tania, Marzetti, Emanuele , Masaldan, Shashank , Masclaux-Daubresse, Celine, Mashek, Douglas G. , Massa, Valentina , Massieu, Lourdes , Masyuk, Anatoliy I. , Masyuk, Tetyana V., Matheu, Ander , Matoba, Satoaki , Matsuzaki, Sachiko , Mattar, Pamela , Mattè, Alessandro , Mauriz, José L., Mauthe, Mario , Maycotte, Paola , Mayer, Johanna , Mazzoni, Cristina , Mazzulli, Joseph R. , McCarty, Nami , McGill, Mitchell R. , McKenna, Sharon L. , McLoughlin, Fionn , McNiven, Mark A., McWilliams, Thomas G. , Medeiros, Tania , Medina, Diego L., Megeney, Lynn A. , Megyeri, Klára , Mehrpour, Maryam , Mehta, Jawahar L. , Meijer, Alfred J., Mejlvang, Jakob , Meléndez, Alicia , Melk, Annette, Memişoğlu, Gönen , Mendes, A.F. , Meng, Delong , Meng, Fei, Mercier, A., Mergny, Jean‐Louis , Merkley, Seth D. , Meske, Volker, Mestre, Ana Cecilia, Metur, Shree Padma, Meyer, C., Meyer, Hemmo , Mi, Wenyi , Mialet‐Perez, Jeanne , Miao, Jun‐Ying, Micale, Lucia , Miki, Yasuo, Milan, Enrico , Milczarek, Małgorzata , Miller, Samuel I. , Millward, Steven W. , Mirzaei, Hamed, Mirzaei, Hamid Reza , Mirzaei, Mehdi , Mishra, Amit , Mishra, Nandita , Mishra, Paras Kumar, Misirkić, Maja , Misasi, Roberta, Misra, Amit , Misso, Gabriella , Mitchell, Claire H. , Mitou, Géraldine, Miura, Tetsuji , Miyazaki, Makoto, Miyazaki, Mitsunori , Miyazaki, Taiga , Miyazawa, Keisuke, Mizushima, Noboru , Mogensen, Trine H. , Mohammadinejad, Reza , Mohamud, Yasir , Mohanty, Abhishek , Möhlmann, Torsten , Moley, Kelle H. , Möller, Andreas, Mollereau, Bertrand , Mollinedo, Faustino, Montagna, Costanza , Monteiro, Mervyn J. , Montella, Andrea , Montes, L. Ruth , Montico, Barbara , Mony, Vinod K., Compagnoni, Giacomo Monzio , Moore, Michael N. , Moosavi, Mohammad Amin , Morales‐Álamo, David , Moratalla, Rosario , Moreira, Paula I. , Morelli, Elena , Moreno-Blas, Daniel , Morgan, Alwena H. , Morin, Fabrice , Morishita, Hideaki , Moriyama, Mariko , Moriyasu, Yuji, Morleo, Manuela , Morselli, Eugenia , Moruno-Manchon, Jose F. , Moscat, Jorge , Motori, Elisa , Moura, Andréa Felinto , Mrakovcic, Maria, Muciño-Hernández, Gabriel, Mukherjee, Anupam , Mukhopadhyay, Subhadip , Levy, Jean M. 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Celeste, Nicoli, Francesco , Nieto‐Díaz, Manuel , Niranjan, Rituraj , Nishimune, Hiroshi , Niso-Santano, Mireia, Nixon, Ralph A. , Nobili, Annalisa , Noda, Takeshi , Nogueira-Recalde, Uxía , Nombela, Iván , Novak, Ivana, Novoa, Beatriz , Nukina, Nobuyuki , Nussbaum-Krammer, Carmen, Nylandsted, Jesper , O’Donovan, Tracey R. , O’Leary, Seónadh M. , O’Rourke, Eyleen J. , O’Sullivan, Mary P. , O’Sullivan, Timothy E., Oddo, Salvatore , Oehme, Ina, Ogawa, Michinaga , Ogier‐Denis, Éric , Ögmundsdóttir, Margrét H. , Öğretmen, Besim , Oh, Goo Taeg , Oh, Seon‐Hee , Oh, Young J. , Ohama, Takashi, Ohashi, Yohei , Ohmuraya, Masaki, Oikonomou, Vasileios , Ojha, Rani , Okazawa, Hitoshi , Oku, M., Oliván, Sara , Oliveira, Jorge M.A. , Ollmann, Michael, Olzmann, James A. , Omari, Shakib , Önal, Gizem, Ondrej, Martin , Ong, Sang‐Bing , Onnis, Anna , Orellana, Juan , Orellana‐Muñoz, Sara , Ortega-Villaizán, María del Mar , Ortiz‐González, Xilma R. , Osiewacz, Heinz D. , Osman, Abdel‐Hamid K. , Otsu, Kinya, Ott, Christiane , Ou, Jing-hsiung James, Outeiro, Tiago F., Öztürk, Melek , Pagès, Gilles, Pahari, Susanta , Pajares, Marta, Pal, Rituraj, Paladino, Simona , Palmieri, Michela , Palmisano, Giuseppe , Pan, Qingjun , Pan, Xin , Panasyuk, Ganna , Pandey, Rahul , Pandey, Udai B., Pandya, Vrajesh , Paneni, Francesco , Pang, Shirley Yin-Yu, Papademetrio, Daniela L. , Papinski, Daniel, Papp, Diana , Park, Hwan Tae , Park, Ji-Man, Park, Jong‐In , Park, Junsoo, Park, Sang-Youel, Pasquier, Adrien , Pasquier, Benoit , Passos, João F. , Pastore, Nunzia , Patschan, Daniel , Pattingre, Sophie , Pedraza‐Alva, Gustavo , Pedraza-Chaverri, Jose, Pedrozo, Zully , Pei, Gang , Pei, Jianming , Peled-Zehavi, Hadas, Pellegrini, Joaquín Miguel , Pelletier, Joffrey , Peñalva, Miguel A., Peng, Di , Peng, Ying , Pennuto, Maria , Pentimalli, Francesca , Pereira, Cláudia MF, Pereira, Gustavo J.S. , Pereira, Lílian Cristina , Almeida, Luís Pereira de , Perera, Nirma D. , Pérez-Lara, Ángel, Pérez‐Oliva, Ana B. , Perl, András , Pestell, Richard G. , Petrache, I., Petrovski, Goran , Pfirrmann, Thorsten , Pfister, Astrid S., Pi, Huifeng , Pickrell, Alicia M. , Picot, Sandy, Pierantoni, Giovanna Maria , Pierre, Philippe , Pierrefite‐Carle, Valérie , Pierzynowska, Karolina , Pietruczuk, Mirosława , Pimentel-Muiños, Felipe X., Pinar, Mario , Pinheiro, Roberta Olmo , Pinkas‐Kramarski, Ronit , Pircs, Karolina , Piya, Sujan , Pizzo, Paola , Platta, Harald W. , Plomann, Markus , Pocock, Roger , Pöggeler, Stefanie , Pohl, Christian, Poirot, Marc , Poletti, Angelo , Ponpuak, Marisa , Popelka, Hana , Popova, Bilyana , Porta, Helena, Alcón, Soledad Porte , Portilla-Fernández, Eliana , Potts, Malia B. , Powers, Ted, Prahlad, Veena , Prajsnar, Tomasz K. , Praticò, Domenico , Prencipe, Rosaria, Priault, Muriel , Proikas‐Cezanne, Tassula , Puertollano, Rosa , Puglielli, Luigi, Pulinilkunnil, Thomas , Puri, Deepika , Puri, Rajat, Puyal, Julien , Qi, Yongmei , Quadrilatero, Joe , Quarleri, Jorge, Raben, Nina, Rabinowich, Hannah, Ragona, Debora, Rahmati, Marveh , Raia, Valeria, Raimundo, Nuno , Rajasekaran, Namakkal-Soorappan, Rao, Sriganesh Ramachandra , Rami, Abdelhaq, Ramírez‐Pardo, Ignacio , Ramsden, D. , Randow, Felix , Ranieri, Danilo , Rao, Hai , Rao, Rekha , Rathore, Sumit , Ratnayaka, J. 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M. , Soldati, Thierry , Soler, Rosa M. , Somarelli, Jason A. , Sonawane, Avinash , Song, Fuyong, Song, Hyun Kyu , Song, Kunhua , Sorice, Maurizio , Soukas, Alexander A. , Soukup, Sandra‐Fausia , Sousa, Diana , Sousa, Nadia, Bharath, M. M. Srinivas , Clair, Daret St., Stagni, Venturina, Staiano, Leopoldo , Stankov, Metodi V. , Stathopulos, Peter B. , Stefan, Katja, Stefan, Sven Marcel , Stefanis, Leonidas, Steffan, Joan S. , Steinkasserer, Alexander , Stenmark, Harald, Sterneckert, Jared , Stevens, Craig , Storch, Stephan , Strappazzon, Flavie , Strohecker, Anne M. , Stupack, Dwayne G., Su, Huanxing , Su, Ling‐Yan , Suarez-Fontes, Ana Márcia , Subirada, Paula V., Sudhandiran, Ganapasam, Sue, Carolyn M. , Sui, Xinbing , Summers, Corey M., Sun, Guangchao , Sun, Zhongjie , Sunahara, Karen K. S. , Susztak, Katalin, Šutovský, Peter , Suzuki, Hidekazu , Sweeney, Gary , Symons, J. David , Sze, Stephen Cho Wing , Szewczyk, Nathaniel J. , Tabęcka-Łonczynska, Anna, Tabolacci, Claudio , Taegtmeyer, Heinrich, Tagaya, Mitsuo , Tai, Haoran , Tait, Stephen W. G., Takahashi, Yoshinori , Tam, Chit , Tam, Shing Yau , Tampellini, Davide , Tamura, Atsushi , Tan, Eng-King, Tan, Ya‐Qin , Tanaka, Masaki , Tang, Daolin , Tang, Jingfeng , Tang, Tie-Shan , Tao, Zhipeng , Taouis, Mohammed , Tavernarakis, Nektarios, Taylor, Allen, Teixeira, Natércia , Tekirdağ, Kumsal Ayşe, Tencomnao, Tewin , Tenreiro, Sandra , Tharaux, Pierre‐Louis , Thedieck, Kathrin , Thekkinghat, Arvind A. , Thinwa, Josephine , Thirumalaikumar, Venkatesh P. , Thomes, Paul G. , Thorburn, Andrew , Thum, Thomas, Thumm, Michael , Tian, Ling, Tichý, Aleš , Timmerman, Vincent , Titorenko, Vladimir I. , Toivonen, Janne M. , Tomaipitinca, Luana , Tomar, Dhanendra , Tomás‐Zapico, Cristina , Tomić, Sergej , Tong, Chao, Tong, Xin , Torgersen, Maria L., Torii, Satoru , Torres-López, Liliana , Torriglia, Alicia , Towers, Christina G. , Towns, Roberto, Tran, Quynh‐Giao , Travassos, Leonardo H. , Tremel, Shirley , Trougakos, Ioannis P., Tsao, Betty P. , Tse, Tak Fu, Tsvetkov, Andrey S. , Tumbarello, David A. , Tyler, Jessica K., Tyutereva, Elena V. , Uchiyama, Yasuo , Ugun‐Klusek, Aslihan , Uhlig, Holm H. , Ułamek-Kozioł, Marzena, Ulasov, Ilya V. , Umekawa, Midori, Ungermann, Christian , Urbe, Sylvie, Uribe-Carretero, Elisabet , Uversky, Vladimir N. , Vaccaro, María I. , Vahsen, Björn F. , Vakifahmetoglu-Norberg, Helin, Valdor, Rut , Valente, Maria João , Valko, Ayelén , Vallée, Richard, Valverde, Ángela M. , Berghe, Greet Van den, Veen, Stijn van der , Kaer, Luc Van , Loosdregt, Jorg van , Wijk, Sjoerd J. L. van , Vandenberghe, Wim , Vanhorebeek, Ilse , Vannier-Santos, Marcos A., Vannini, Nicola , Vanrell, M. Cristina, Vantaggiato, Chiara , Varela‐Nieto, Isabel , Varga, Máté , Vasconcelos, M. Helena , Vats, Somya , Vega-Rubín-de-Celis, Silvia , Velasco, Guillermo , Velázquez, Ariadna P., Vellai, Tibor , Vellenga, Edo , Verdier, Mireille , Verginis, Panayotis , Vergne, Isabelle , Verkade, Paul , Verma, Manish , Verstreken, Patrik , Vervliet, Tim , Vervoorts, Jörg , Víctor, Víctor M., Vidoni, Chiara , Vieira, Otília V. , Vierstra, Richard D., Viganò, Sonia , Vihinen, Helena , Vijayan, Vinoy, Vila, Miquel , Villalba, José M., Villalobo, Antonio , Villarejo‐Zori, Beatriz , Vincent, Olivier , Vindis, Cécile , Viret, Christophe , Vocadlo, David J. , Voitsekhovskaja, Olga V. , Volonté, Cinzia , Volta, Mattia , Vomero, Marta , Haefen, Clarissa von, Vooijs, Marc , Voos, Wolfgang , Vučićević, Ljubica , Waguri, Satoshi , Waite, Kenrick A., Wakatsuki, Shuji , Walker, David W., Walker, Mark J. , Walter, Jochen, Wandosell, Francisco , Wang, Bo , Wang, Chao-Yung, Wang, Chen , Wang, Chenran, Wang, Chenwei , Wang, Cun-Yu, Wang, Fengming, Wang, Han, Wang, Hexiang , Wang, Hong‐Gang , Wang, Jianrong, Wang, Jigang , Wang, Jun-Dong , Wang, Kui , Wang, Lianrong, Wang, Liming , Wang, Maggie Haitian, Wang, Meiqing , Wang, Nanbu , Wang, Pengwei , Wang, Ping , Wang, Ping, Wang, Q., Wang, Qiong , Wang, Wentao , Wang, Xinnan, Wang, Xuejun , Wang, Yan, Wang, Yanchang , Wang, Yanzhuang , Wang, Yihua , Wang, Yu , Wang, Yuqi , Wang, Zhe, Wang, Zhenyu , Wang, Zhouguang , Watanabe, Eizo, Watchon, Maxinne , Wawrzyńska, Anna , Weaver, Timothy E., Węgrzyn, Grzegorz, Wehman, Ann M. , Wei, Huafeng , Wei, Taotao , Wei, Yongjie, Weiergräber, Oliver H. , Weihl, Conrad C., Weindl, Günther , Weiskirchen, Ralf , Wen, Runxia H. , Werner, Antonia, Weykopf, Beatrice , Whitton, J. Lindsay , Wiktorska, Katarzyna , Wildenberg, Manon E. , Wileman, Tom, Wilkinson, Simon , Williams, Brett, Williams, Robin S. B. , Williamson, Peter R. , Wilson, Richard A. , Winsor, Nathaniel J. , Wodrich, Harald , Woehlbier, Ute , Wollert, Thomas , Wong, Richard W., Wong, Vincent Kam Wai , Wong, W. Wei-Lynn, Wu, Anguo , Wu, Kenneth K., Wu, Shan‐Ying , Wu, William Ka Kei , Wu, Shufang, Wu, Xiaoqing , Wu, Yao‐Wen , Wu, Yihua , Xavier, Ramnik J. , Xia, Hongguang , Xia, Lixin , Xia, Zhengyuan , Ge, Xiang , Xiang, Jin , Xiang, Mingliang , Xiang, Wei , Xiao, Guozhi , Xiao, Hengyi , Xiao, Hongtao , Xiao, Jian, Xiao, Lan , Xiao, Shi , Xiao, Yin , Xie, Baoming, Xie, Zhiping , Xie, Min , Xie, Yuxiang , Xie, Zhonglin, Xilouri, Maria , Xu, En , Xu, Jin‐Rong , Xu, Liang , Xu, Xiulong , Xue, Yu , Yakhine-Diop, Sokhna M. S. , Yamaguchi, Masamitsu , Yamamoto, Ai , Yamashina, Shunhei, Yan, Shengmin , Yan, Shian-Jang, Yan, Zhen , Yang, Chuanbin , Yang, Dun-Sheng, Yang, Huan , Yang, Huang-Tian, Yang, Hui , Yang, Jing , Yang, Jingyu , Yang, Ling , Liu, Yang , Yang, Ming , Yang, Seungwon, Yang, Shu , Yang, Shun-Fa , Yang, Wannian, Yang, Wei , Yang, Xiaoyong , Yang, Yi , Yao, Xiaoqiang , Yao, Yong-Gang , Yao, Yong-ming, Yasui, Takahiro , Yazdankhah, Meysam, Yi, Cong , Yin, Xiao-Ming , Yin, Yanhai , Yin, Zhangyuan , Yin, Ziyi , Ying, Meidan , Ying, Zheng, Yip, Calvin K. , Yiu, Stephanie Pei Tung , Yoo, Young Hyun , Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan , Yu, Haiyang , Yu, Jun, Li, Yu , Yu, Ming‐Lung , Yu, Seong-Woon, Yu, Victor C. , Yu, Zhengping, Yuan, Junying , Yuan, Ling‐Qing , Yuan, Shilin , Yuan, Yanggang , Yuan, Zengqiang , Yue, Jianbo , Yue, Zhenyu , Yung, Raymond , Zacks, David, Zaffagnini, Gabriele , Zambelli, Vanessa O. , Zanella, Isabella , Zang, Qun S. , Zanivan, Sara , Zappavigna, Silvia , Zaragoza, P. , Zarbalis, Konstantinos S., Zarebkohan, Amir , Zarrouk, Amira , Zeitlin, Scott, Zeng, Jialiu , Zeng, Judeng , Žerovnik, Eva , Zhan, Lixuan , Zhang, Donna D., Zhang, Hong , Zhang, Honghe , Zhang, Huafeng , Zhang, Huaye, Zhang, Huiling , Zhang, Jianbin , Zhang, Jingpu , Zhang, Kalin Yanbo , Zhang, Leshuai W. , Zhang, Lu , Zhang, Luoying , Zhang, Menghuan, Zhang, Peng , Zhang, Sheng , Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei , Zhang, Xiaoyan , Zhang, Xin , Zhang, Xinxin , Zhang, Yang, Zhang, Yi , Zhang, Yingdong , Zhang, Yuanyuan , Zhang, Yuchen , Zhang, Zhe , Zhang, Zhibing , Zhang, Zili , Zhao, Haobin, Zhao, Lei , Zhao, Shuang , Zhao, Tongbiao , Zhao, Ying, Zhao, Yongchao , Zhao, Yongliang , Zhao, Yuting , Zheng, Guoping , Zheng, Kai, Zheng, Ling , Zheng, Shizhong , Zheng, Xi‐Long , Zheng, Zu‐Guo , Zhivotovsky, Boris, Zhong, Qing , Zhou, Ao, Zhou, Ben , Zhou, Cefan , Zhou, Gang , Zhou, Hongbo , Zhou, Kailiang, Zhou, Rongjia , Zhou, Yanshuang, Zhou, Yinghong , Zhou, Yubin , Zhou, Zhengyu, Zhou, Zhou , Zhu, Binglin , Zhu, Changlian , Zhu, Guo‐Qing , Zhu, Haining , Zhu, Hongxin, Zhu, Yanping , Zhu, Yushan , Zhuang, Haixia , Zhuang, Xiaohong , Zimmermann, Christine , Żołądek, Teresa , Zong, Wei‐Xing, Zorov, Dmitry B. , Zorzano, Antonio, Zou, Weiping, Zou, Zhen , Zou, Zhengzhi, Zuryn, Steven , Kenchappa, Chandra Shekar, Li, Zuguo , Lin, Yong , Sluimer, Judith C. , Stallings, Christina L. , Tong, Chun-Kit, Wang, Ping , Hu, Bo , Lee, Edward B. , Tse, Hung‐Fat , Suszták, Katalin , Lei, Yu Leo , Yu, M-L , Dai, Yun , Bartolome, Alberto , Brown, Rhoderick E , Passos, João F , Paneni, Francesco , Sahin, Özgür , Pereira de Almeida, Luis , Ren, Jun , Bornhauser, Beat , Kumar, Sharad , Sampaio-Marques, Belém , Ludovico, Paula , Luftig, Micah , Begun, Jakob , Krasnodembskaya, Anna D , Dafsari, Hormos Salimi , Chevet, Eric , Tse, Hung-Fat , Barmada, Sami , Ebrahimi-Fakhari, Darius , Cavadas, Claudia , Sue, Carolyn M , Cardenal-Muñoz, Elena , Lee, Edward B , Golebiewska, Anna , Calbet, Jose A L , Boya, Patricia , Maday, Sandra , Klionsky, Daniel J. , Abdelfatah, Sara , Abdoli, Asghar , Agarwal, Anupam , Ahmed, Zubair M. , Alcocer‐Gómez, Elísabet , Ali, Muhammad , Al‐Bari, Md. Abdul Alim , Aliwaini, Saeb H. , Alizadeh, Javad , Almacellas, Eugènia , Almasan, Alexandru , Alonso, G. , Altieri, Dario C. , Andersen, Stig Uggerhøj , Andrade-Silva, Magaiver , Angelini, Sabrina , Apostolova, Nadezda , Arasaki, Kohei , Araújo, Wagner L. , Arden, Catherine , Arimoto, Hirokazu , Armstrong-James, Darius P. H. , Pelloquin, Laetitia , Aschner, Michael , Ashrafizadeh, Milad , Autelli, Riccardo , Aveic, Sanja , Avin‐Wittenberg, Tamar , Ayton, Scott , Backues, Steven K. , Bae, Dong-Hun , Bae, Ok‐Nam , Baek, Ahruem , Baek, Seung‐Hoon , Baek, Sung Hee , Bai, Jie , Bai, Yidong , Baldari, Cosima T. , Balduini, Walter , Ballabio, Andrea , Banerjee, Sreeparna , Bao, Yan , Baptista, Maurı́cio S. , Barreto, George Emilio , Basagoudanavar, Suresh H. , Bast, Robert C. , Basu, Alakananda , Batoko, Henri , Batten, Isabella , Behrens, Georg M. N. , Bei, Roberto , Behl, Christian , Bello‐Morales, Raquel , Beltrán, Sebastián , Bergami, Matteo , Bergmann, Andreas , Berthoux, Lionel , Bhattacharya, Resham , Bhattacharyya, Shalmoli , Bhutia, Sujit Kumar , Bi, Lanrong , Birgisdottir, Åsa Birna , Bjørkøy, Geir , Blomgren, Klas , Boada-Romero, Emilio , Boesze‐Battaglia, Kathleen , Bonifacino, Juan S. , Boone, Brian A. , Borthakur, Gautam , Bosch, Jürgen , Bose, Santanu , Botana, Luis Miguel , Boulton, Michael E. , Bourdenx, Mathieu , Brackney, Doug E. , Brandts, Christian , Braun, Ralf J. , Braus, Gerhard H. , Bravo, Roberto , Brody, Steven L. , Brown, Carolyn Nicole , Brumell, John Hunter , Brunetti‐Pierri, Nicola , Buitrago‐Molina, Laura Elisa , Buraschi, Simone , Buch, Shilpa J. , Butturini, Elena , Cairó, Montserrat , Caldwell, Kim A. , Campbell‐Valois, François‐Xavier , Campello, Silvia , Campesi, Ilaria , Almeida, Danilo Cândido de , Canesi, Laura , Caraglia, Michele , Carchman, Evie H. , Carmona‐Gutiérrez, Didac , Carnevali, Oliana , Carrier, Lucie , Carroll, Bernadette , Carter, A. Brent , Casas, Caty , Castillo, Eliseo F. , Castro‐Caldas, Margarida , Castro‐Obregón, Susana , Catz, Sergio , Cayuela, María Luisa , Cecarini, Valentina , Cecconi, Francesco , Cenci, Simone , Ceperuelo‐Mallafré, Victòria , Cervia, Davide , Chae, Han–Jung , Chakrabarti, Oishee , Chan, Edmond Y. W., Chan, Edward D. , Chandra, Partha Kumar , Chang, Chih‐Peng , Chang, Chunmei , Chapman, Tracey , Chen, Guang‐Chao , Chen, Leilei , Chen, Lin , Chen, Quan , Chen, Ruey‐Hwa , Chen, Shi , Chen, Wei‐Qiang , Chen, Xu , Chen, Yu-Jen , Chen, Yujie , Chen, Zhi , Chen, Zhijian J. , Chen, Zhixiang , Cheng, Hanhua , Cheng, Jun , Cheng, Shi‐Yuan , Cheng, Wei Nee , Cheng, Xiaodong , Chen, Zhong , Cheong, Heesun , Chernyak, Boris V. , Chi, Richard J., Chiang, Aks , Chiarelli, Roberto , Chu, Charleen T. , Chung, Seockhoon , Cianfanelli, Valentina , Cifuentes, Mariana , Cirone, Mara , Clague, Michael J. , Cohen, Ehud , Cohen, Mickaël M. , Čolić, Miodrag J , Combaret, Lydie , Comincini, Sergio , Conte, Andrea, Conti, Fabrizio , Coppens, Isabelle , Corasaniti, Maria Tiziana , Corkery, Dale , Cordes, Nils , Cortese, Katia , Coto‐Montes, Ana M. , Crack, Peter John , Crespo, José L. , Cuadrado, Antonio , Cui, Jun , Cui, Yong , D’Arcangelo, Daniela , D’Lugos, Andrew C. , Dagda, Ruben Karim , Dagdas, Yasin , Daμμe, Markus , Dantuma, Nico P. , Darling, April L. , Dasarathy, Srinivasan , Daumke, Oliver , Davis, Tanja , Amicis, Francesca De , Felice, Francesca De , Franceschi, Lucia De , Milito, Angelo De , Nunzio, Cosimo De , Santi, Mauro De , Debnath, Jayanta , DeBosch, Brian J. , DeGregori, James V. , Rio, Gabriel del , Delbridge, Lea M.D. , Delpino, M. Victoria , Demarchi, Francesca , Dembitz, Vilma , Deng, Zhiqiang , Denton, Donna , Der, Channing J , Deretić, Vojo , Dhiman, Rohan , Bernardo, Diego di , Cristina, Manlio Di , Nardo, Alessia Di, Sano, Federica Di , Diallinas, George , Diaz-Araya, Guillermo, Đikić, Ivan , Ding, Wen‐Xing , Dini, Luciana , Dionne, Marc , Diwan, Abhinav , Dixon, Ian , Djavaheri‐Mergny, Mojgan , Dobrinski, Ina , Dobrovinskaya, Oxana R. , Dobrowolski, Radek , Dobson, Renwick C. J. , Donadelli, Massimo , Dong, Bo, Dötsch, Volker , Dou, Huan , Dridi, Sami , Du, Caigan , Du, Li‐Lin , Dubrovska, Anna , Dunlop, Elaine A. , Dwarakanath, Bilikere Srinivasa Rao , Eftekharpour, Eftekhar , Eichinger, Ludwig , Eissa, N. Tony , Eissa, Sanaa , El‐Naggar, Shahenda , Eliopoulos, Aristides G. , Elks, Philip M. , Emerling, Brooke M. , Engelbrecht, Anna‐Mart , Escobar‐Henriques, Mafalda , Fabriàs, Gemma , Fabrizi, Cinzia , Falkenburger, Björn H. , Fan, Yanbo , Fanto, Manolis , Feng, Du , Feng, Yibin , Feng, Yuchen , Fernández-Checa, José Carlos , Filippi‐Chiela, Eduardo Cremonese , Filomeni, Giuseppe , Fineschi, Vittorio , Flamigni, Flavio , Follo, Carlo , Fon, Edward A , Fornai, Francesco , Fraldi, Alessandro , Franco, Brunella , Franco, Rodrigo , Friedman, Scott L. , Frühbeck, Gema , Fujita, Naonobu , Fujiwara, Yuuki , Fukuda, Mitsunori , Furic, Luc , Fusco, Carmela , Galluzzi, Lorenzo, Gan, Boyi , Gao, Hui , Gao, Shou‐Jiang , Gargini, Ricardo , Garry, Robert F. , Ge, Liang , Ge, Wanzhong , Gelfi, Cecilia , Gentle, Ian Edward , Gewirtz, David A , Ghigo, Alessandra , Giampietri, Claudia , Gibson, Spencer B. , Giniger, Edward , Giorgi, Carlotta , Girão, Henrique , Goldstone, David C. , Gomez‐Puerto, Maria Catalina , Goñi, Félix M. , González‐Hernández, Tomás , Gorbatyuk, Marina S. , Goruppi, Sandro , Gottlieb, Roberta A. , Gozes, Illana , Green, Douglas R. , Grinstaff, Mark W. , Grune, Tilman , Guntur, Anyonya R. , Guo, Lian‐Wang , Gupta, Shashi Kumar , Gustafsson, Åsa B. , Haapasalo, Annakaisa , Hadano, Shinji , Hafrén, Anders , Hall, Belinda S. , Hamann, Andréa , Han, Weidong , Hanson, Phyllis I. , Haroon, Nigil , Harris, James , Hasegawa, Takafumi , Nagoor, Noor Hasima , Hay, Bruce A. , Hayrabedyan, Soren , He, Yu‐Ying , Helgason, G. Vignir , Hergovich, Alexander , Hernández–Gea, Virginia , Heussler, Volker Theo , Hlavacek, William S. , Hobbs, G. Aaron , Hochstrasser, Mark , Hofman, Paul , Holmberg, Carina I. , Hombrebueno, José R. , Hoppe, Thorsten , Horos, Rastislav , Hoshida, Yujin , Hsu, Hsin‐Yun , Hu, Li‐Fang , Hu, Ming Chang , Hu, Ronggui , Hu, Yu‐Chen , Hua, Fang , Hua, Jinlian, Hua, Yingqi , Huang, Canhua , Huang, Chuanxin , Huang, Kun , Huang, Rui , Huber, Tobias Bruno , Humbert, Magali , Hussey, Patrick J. , Hwang, Hui‐Yun , Hwang, Seungmin , Imai, Yuzuru , Iovanna, Juan , Ippolito, Giuseppe , Irazoqui, Javier E. , Ishaq, Mohd, Ishikawa, Makoto , Isidoro, Ciro , Izumi, Masanori , Jäättelä, Marja , Jabir, Majid Sakhi , Jackson, William T. , Jacomin, Anne‐Claire , Jakobi, Arjen J. , Jantsch, Jonathan , Jassey, Alagie , Jean, Steve , Jendelová, Pavla , Jewell, Jenna L. , Ji, Jing , Jiang, Liwen , Jin, Eun‐Jung , Jin, Hongchuan , Jin, Meiyan , Jo, Eun‐Kyeong , Johansen, Terje , Johnson, Gail V.W. , Jolly, Mohit Kumar , Joosten, Leo A. B. , Jordán, Joaquı́n , Joseph, Bertrand , Ju, Dianwen , Ju, Jeong-Sun , Ju, Jingfang , Judith, Delphine , Jung, Yong‐Keun , Kaarniranta, Kai , Kabuta, Tomohiro , Kahana, Alon , Kaminskyy, Vitaliy O. , Kanasaki, Keizo , Kanthasamy, Anumantha G. , Karamouzis, Michalis V. , Karmakar, Parimal , Katare, Rajesh , Kaufmann, Stefan H. E. , Kaushik, Susmita , Kawasaki, Kiyoshi, Ke, Po‐Yuan , Keating, Damien J. , Kehrl, John H. , Keller, Christian W. , Kemper, Jongsook Kim , Kermorgant, Stéphanie , Ketteler, Robin , Khambu, Bilon , Kim, Deok Ryong, Kim, Eun Young , Kim, Jin Kyung , Kim, Jin‐Hoi , Kim, Ju Hwan , Kim, Keun Il , Kim, Peter Kijun , Kinghorn, Kerri J. , Kirkin, Vladimir , Киселев, С. Л. , Kittler, Josef T. , Knorr, Roland L. , Ko, Ben C.B. , Ko, Jiunn‐Liang , Kobayashi, Hotaka , Koenig, Ulrich , Koike, Masato , Kohlwein, Sepp Dieter , Komatsu, Masaaki , Kopp, Benjamin T. , Korcsmaros, Tamas Douglas , Korolchuk, Viktor I. , Kotler, Mónica L. , Koukourakis, Michael Ioannis , Kovács, Tibor, Koya, Daisuke , Kozako, Tomohiro , Krämer, Helmut , Kroemer, Guido , Ktistakis, Nicholas T. , Kuchitsu, Kazuyuki , Kumar, Ashok , Kumar, Deepak, Kundu, Mondira , Kurgan, Lukasz , Kutateladze, Tatiana G. , Kwon, Ho Jeong , Kwon, Taeg Kyu , Kyrmizi, Irene , Spada, Albert R. La , Lai, Zhibing, Lamark, Trond , Lane, Jon D. , Lang, Charles H. , Lange, Carsten, Langel, Ülo , Lapaquette, Pierre , LaRusso, Nicholas F. , Lastres‐Becker, Isabel , Lavandero, Sergio , Law, Hkw , Layfield, Robert , Leduc‐Gaudet, Jean‐Philippe , Lee, He-Jin, Lee, Jae Man , Lee, Jun Hee , Lee, Seung‐Jae , Lee, Ying‐Ray , Lefebvre, Christophe , Legouis, Renaud , Leitinger, Gerd , Lenz, Heinz Josef, León, Yolanda, Leopoldino, Andréia Machado , Leung, Chi-Ting, Levine, Beth , Li, Jing , Li, Ke, Li, Min , Li, Min , Li, Pin‐Lan , Li, Tiangang , Li, Zhiqiang, Lian, Jiqin , Liang, Chengyu, Liang, Qiangrong , Liao, Mingzhi , Lilly, Mary A. , Lin, Liang , Lin, Pei‐Hui , Lin, Xueying , Linden, Rafael , Ling, Shuo‐Chien , Lingor, Paul , Linnemann, Amelia K , Liou, Yih‐Cherng , Lira, Vitor Agnew , Liu, Chunfeng , Liu, Cui Hua , Liu, Hao , Liu, Hsiao‐Sheng , Liu, Julia C. , Liu, Longhua , Liu, Meilian , Liu, Qin , Liu, Xiao-Hong, Liu, Xiaodong , Liu, Xingguo , Liu, Xuedong , Liu, Yang, Liu, Yang, Lizard, Gérard , Llorente, Alicia , Long, Qi , Long, Yun Chau, López, Manuela G. , Lőrincz, Péter , Lovat, Penny E. , Lu, Jin‐Jian , Lum, Julian J., Lünemann, Jan D. , Luo, Shouqing , Ma, Changle , Ma, Mengxiao , Ma, Ning‐Fang , Macián, Fernando , MacKeigan, Jeffrey P. , Majello, Barbara , Malorni, Walter , Mandell, Michael A. , Manjili, Masoud H. , Manjithaya, Ravi R. , Manque, Patrício , Manzoni, Claudia , Mao, Kai, Marconi, Anna Maria , Margeta, Marta , Marinelli, Oliviero , Marshall, Richard Scott , Marten, Mark R. , Martens, Sascha , Martin, Sara, Martín-Acebes, Miguel A. , Martín‐Burriel, Inmaculada , Martina, José A. , Martinet, Wim , Martinez, Jennifer , Martínez‐Velázquez, Moisés , Martinez-Lopez, Nuria, Martins‐Marques, Tânia , Masclaux‐Daubresse, Céline , Masson, Glenn Robert , Masuelli, Laura , Masyuk, Tetyana V., Matarrese, Paola , Mattoscio, Domenico , Mauriz, Jose Luis , Mauvezin, Caroline , Maverakis, Emanual Michael , Mazzoccoli, Gianluigi , McDonald, Christine , McLaughlin, BethAnn , Mechta‐Grigoriou, Fatima , Meijer, Annemarie H. , Meng, Tian, Menna‐Barreto, Rubem F. S. , Menon, Manoj B., Mercer, Carol A. , Mercier, Anne E., Merighi, Adalberto , Merla, Giuseppe , Miller, Dana L. , Miller, Silke , Milošević, Ira , Minina, Elena A. , Mirzaei, Mehdi, Mishra, Paras Kumar , Miyamoto, Shigeki, Miyazawa, Keisuke, Mograbi, Baharia , Mohanty, Abhishek , Mohapatra, Sipra , Mohmmed, Asif , Moles, Anna , Molinari, Maurizio , Mollace, Vincenzo , Møller, Andreas Buch , Mora, Ana Lucia , Mora, Marina, Morelli, Elena, Moreno, Sandra , Moresi, Viviana , Morga, Benjamín , Moritz, Orson L. , Moriyama, Mariko, Mostowy, Serge , Moustaïd‐Moussa, Naïma , Muller, Sylviane , Munjal, Ashok Kumar , Muñoz‐Cánoves, Pura , Münz, Christian , Muratori, Claudia, Murphy, John Patrick , Nabissi, Massimo , Nah, Jihoon , Nakagawa, Ichiro, Nakatogawa, Hitoshi , Nardacci, Roberta , Narita, Masashi , Neri, Luca Maria , Neufeld, Thomas P. , Nezis, Ioannis P. , Ni, Hong‐Min , Nicolao, María Celeste , Nilsson, Per Gunnar , Ning, Shunbin , Nóbrega, Clévio , Nolan, Trevor M. , Novak, Ivana, Nozawa, Takashi , Nussbaum-Krammer, Carmen I. , O’Sullivan, Timothy E., Oehme, Ina , Ohmuraya, Masaki , Okamoto, Koji , Oku, Masahide, Omary, M. 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G.

Autophagy | March 24, 2021 | Volume: 17 | Issue: 1 | Pages: 1-382

10.1080/15548627.2020.1797280 Get It

Pharmacological targeting of the Aurora A and histone 3 lysine 9 methyltransferase pathways in pancreatic cancer.
Salmonson, Ann, Missfeldt, Mckenna, Assuncao, Thiago de, Bintz, Jennifer , Lomberk, Gwen , Lomberk, Gwen L , Mathison, Angela , Iovanna, Juan , Huebert, Robert C.

Journal of Clinical Oncology | September 6, 2018 | Volume: 34 | Issue: 15_suppl | Pages: e15715-e15715

10.1200/jco.2016.34.15_suppl.e15715 Get It

Abstract 4396: Multiomics assessment of the cancer and stromal compartments of patient-derived pancreatic xenografts reveals clinically-relevant subtypes and novel targeted therapies
Marisa, Laëtitia , Loncle, Céline, Gayet, Odile , Moutardier, Vincent, Giovannini, Marc, Bian, Benjamin , Bigonnet, Martin , Rubis, Marion , Elarouci, Nabila , Armenoult, Lucile, Duconseil, Pauline , Ouaïssi, Mehdi , Maignan, Aurélie, Lomberk, Gwen , Ewald, Jacques , Bories, Erwan, Gonçalves, Anthony , Secq, Véronique, Garcia, Stéphane, Grandval, Philippe , Barraud-Blanc, Marine, Norguet, Emmanuelle, Gilabert, Marine , Roques, Julie, Calvo, Ézéquiel, Vasseur, Sophie , Reyniès, Aurélien de , Nicolle, Rémy , Blum, Yuna , Turrini, Olivıer , Ayadi, Mira , Gasmi, Mohamed , Boher, Jean‐Marie , Garnier, Jonathan , Poizat, Flora , Raoul, Jean‐Luc , Delpéro, Jean‐Robert , Guillaumond, Fabienne , Urrutia, Raúl , Dusetti, Nelson , Iovanna, Juan , Lomberk, Gwen L , de Reynies, Aurélien

Cancer Research | July 31, 2017 | Volume: 77 | Issue: 13_Supplement | Pages: 4396-4396

10.1158/1538-7445.am2017-4396 Get It

Abstract Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. In this work, 29 PDX were obtained from either surgery or endoscopic ultrasound-guided fine needle aspirate of pancreatic adenocarcinoma. The extensive genomic profiling of these pancreatic PDX, revealed two clinically-relevant subtypes having broad similarities with human primary tumors. These subtypes are defined by highly specific DNA methylation and transcriptomic profiles (mRNA, miRNA or lncRNA) but are not distinguishable by exonic mutations or copy number aberrations. Moreover, by specifically analyzing the stroma transcriptome, as defined by the expression of murine transcripts, we found that it is able to stratify the patients with the same efficiency than the analysis of grafted human tumor cells. This finding suggest that transformed pancreatic cells drive the composition of their own stroma. Finally, the multiomics analysis pinpoints novel therapeutic targets, one of which we demonstrate to be an efficient method for treating pancreatic cancer. Overall, we show that PDX are trustworthy pre-clinical models of pancreatic adenocarcinoma including of unresectable tumors. Their multiomics profiling allow the independent analysis of the uncontaminated cancer or stromal compartments and discloses several original therapeutics targets. Citation Format: Remy Nicolle, Yuna Blum, Laetitia Marisa, Celine Loncle, Odile Gayet, Vincent Moutardier, Olivier Turrini, Marc Giovannini, Benjamin Bian, Martin Bigonnet, Marion Rubis, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Pauline Duconseil, Mohamed Gasmi, Mehdi Ouaissi, Aurélie Maignan, Gwen Lomberk, Jean-Marie Boher, Jacques Ewald, Erwan Bories, Jonathan Garnier, Anthony Goncalves, Flora Poizat, Jean-Luc Raoul, Veronique Secq, Stephane Garcia, Philippe Grandval, Marine Barraud-Blanc, Emmanuelle Norguet, Marine Gilabert, Jean-Robert Delpero, Julie Roques, Ezequiel Calvo, Fabienne Guillaumond, Sophie Vasseur, Raul Urrutia, Aurélien de Reyniès, Nelson Dusetti, Juan Iovanna. Multiomics assessment of the cancer and stromal compartments of patient-derived pancreatic xenografts reveals clinically-relevant subtypes and novel targeted therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4396. doi:10.1158/1538-7445.AM2017-4396
Abstract 4060: Pharmacological targeting of the Aurora A and Histone 3 lysine 9 methyltransferase pathways in pancreatic cancer induces mitotic catastrophe
Salmonson, Ann, Missfeldt, Mckenna, Assuncao, Thiago de, Bintz, Jennifer , Christensen, Trace , Kossak, Sarah, Nair, Asha, Lomberk, Gwen , Mathison, Angela , Iovanna, Juan , Huebert, Robert C. , Lomberk, Gwen L

Cancer Research | July 31, 2017 | Volume: 77 | Issue: 13_Supplement | Pages: 4060-4060

10.1158/1538-7445.am2017-4060 Get It

Abstract By regulating gene expression networks that mediate neoplastic behavior, epigenetic protein complexes are the ultimate effectors of oncogenic pathways. This hierarchical position of epigenetic pathways within the mechanisms that regulate cancer makes them ideal candidates for therapeutic targets. The current work was designed to characterize the role of the K9H3 Histone Methyltransferase (HMT) pathway in mediating oncogenic signals downstream of Aurora Kinase A (AurkA), with the goal of designing efficient combinatorial therapies against PDAC. Affinity protein purification, combined with mass spectrometry, demonstrates that HP1γ isolated from mitotic cells interacts with AurkA and the HMTs, G9a and GLP. We also find that this complex is critical for mitotic progression and cell proliferation. Congruently, treatment of PDAC cells with individual drugs against AurkA or HP1-HMT inhibits cell growth by inducing senescence, a cytostatic response. However, the combination of these agents has a synergistic effect of reducing cell growth in both, monolayer and spheroid cultures to result in a cytotoxic effect. Confocal and electron microscopy, along with cell cycle analysis, demonstrate that the cytotoxic effect of this combination is due to induction of mitotic catastrophe, a distinct form of cell death that occurs during mitosis. Molecularly, the combination of AurkA and HP1-HMT inhibition bypasses G2/M arrest with downregulation of the Chk1-Cdc25c pathway. In vivo treatment of PDAC orthotopic xenografts with the HP1-HMT inhibitor alone demonstrated reduced PDAC growth, and increased efficacy in PDAC growth reduction was observed in combination with the AurkA inhibitor over either individual treatment. Thus, our data demonstrate a novel AurkA-HP1-HMT mitotic pathway that holds promise for potential pharmacological targeting in combinatorial therapy for this malignancy. Citation Format: Angela Mathison, Ann Salmonson, Mckenna Missfeldt, Thiago de Assuncao, Jennifer Bintz, Trace Christensen, Sarah Kossak, Asha Nair, Juan Iovanna, Robert Huebert, Gwen Lomberk. Pharmacological targeting of the Aurora A and Histone 3 lysine 9 methyltransferase pathways in pancreatic cancer induces mitotic catastrophe [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4060. doi:10.1158/1538-7445.AM2017-4060