Coker, Oluwadara
Mayo Clinic
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Citations 1
Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers
Klomp, Jennifer E. , Stalnecker, Clint A. , Bryant, Kirsten L. , Edwards, A. Cole , Drizyte‐Miller, Kristina , Hibshman, Priya S. , Diehl, J. Nathaniel , Lee, Ye S. , Morales, Alexis Jean , Taylor, Khalilah E. , Peng, Sen, Tran, Nhan L. , Prevatte, Alex W., Hover, Laura D. , Hallin, Jill , Chowdhury, Saikat , Coker, Oluwadara , Olson, Peter , Christensen, James G. , Graves, Lee M. , Wennerberg, Krister , Klomp, Jeffrey A , Klomp, Jennifer E , Stalnecker, Clint A , Bryant, Kirsten L , Drizyte-Miller, Kristina , Diehl, J Nathaniel , Lee, Ye S , Morales, Alexis J , Taylor, Khalilah E , Herring, Laura E , Barker, Natalie K , Hallin, Jill , Chowdhury, Saikat , Coker, Oluwadara , Lee, Hey Min , Goodwin, Craig M , Gautam, Prson , Olson, Peter , Christensen, James G , Shen, John P , Kopetz, Scott , Graves, Lee M , Lim, Kian-Huat , Wang-Gillam, Andrea , Wennerberg, Krister , Cox, Adrienne D , Der, Channing J , Tran, Nhan L , Herring, Laura E. , Barker, Natalie K. , Gautam, Prson , Kopetz, Scott , Wang‐Gillam, Andrea , Cox, Adrienne D.
Science | June 6, 2024 | Volume: 384 | Issue: 6700 | Pages: No page available
How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and extracellular signal–regulated kinase (ERK)–dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges substantially from the frequently cited Hallmark KRAS signaling gene signature, is driven predominantly through the ERK mitogen-activated protein kinase (MAPK) cascade, and accurately reflects KRAS- and ERK-regulated gene transcription in KRAS-mutant cancer patients. Integration with our ERK-regulated phospho- and total proteome highlights ERK deregulation of the anaphase promoting complex/cyclosome (APC/C) and other components of the cell cycle machinery as key processes that drive pancreatic ductal adenocarcinoma (PDAC) growth. Our findings elucidate mechanistically the critical role of ERK in driving KRAS-mutant tumor growth and in resistance to KRAS-ERK MAPK targeted therapies.