Citations 1
Abstract 1860: DNA-PK-mediated transcriptional regulation drives tumor progression and metastasis
Goodwin, Jonathan F., Zhao, Shuang , Dylgjeri, Emanuela , Dean, Jeffry L. , Graham, Nicholas , Vashisht, Ajay A., Karnes, R. Jeffrey , Takhar, Mandeep, Tomlins, Scott A. , Sharifi, Nima , Witte, Owen N. , Feng, Felix Y. , Kothari, Vishal , Drake, Justin M , Schiewer, Matthew J. , McNair, Christopher M. , Magee, Michael S. , Den, Robert B. , Zhu, Ziqi , Wohlschlegel, James Akira , Graeber, Thomas G. , Davicioni, Elai , Knudsen, Karen E.
Cancer Research | August 5, 2015 | Volume: 75 | Issue: 15_Supplement | Pages: 1860-1860
Abstract Emerging evidence demonstrates that the DNA repair kinase DNA-PK exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PK functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PK inhibits tumor metastases. Clinical assessment revealed that DNA-PK is significantly elevated in advanced disease, and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PK in advanced tumors is highly activated, independently of DNA damage indicators. Combined, these findings put forth new paradigms for DNA-PK function, identify DNA-PK as a potent driver of tumor progression and metastases, and nominate DNA-PK as a therapeutic target for advanced malignancies. Citation Format: Jonathan F. Goodwin, Vishal Kothari, Justin M. Drake, Shuang Zhao, Emanuela Dylgjeri, Jeffry L. Dean, Matthew J. Schiewer, Christopher McNair, Michael S. Magee, Robert B. Den, Ziqi Zhu, Nicholas A. Graham, Ajay A. Vashisht, James A. Wohlschlegel, Thomas G. Graeber, R Jeffrey Karnes, Mandeep Takhar, Elai Davicioni, Scott A. Tomlins, Nima Sharifi, Owen N. Witte, Felix Y. Feng, Karen E. Knudsen. DNA-PK-mediated transcriptional regulation drives tumor progression and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1860. doi:10.1158/1538-7445.AM2015-1860