| Literature DB >> 26175416 |
Jonathan F Goodwin1, Vishal Kothari2, Justin M Drake3, Shuang Zhao2, Emanuela Dylgjeri1, Jeffry L Dean1, Matthew J Schiewer1, Christopher McNair1, Jennifer K Jones1, Alvaro Aytes4, Michael S Magee5, Adam E Snook5, Ziqi Zhu6, Robert B Den7, Ruth C Birbe8, Leonard G Gomella9, Nicholas A Graham10, Ajay A Vashisht11, James A Wohlschlegel11, Thomas G Graeber12, R Jeffrey Karnes13, Mandeep Takhar14, Elai Davicioni14, Scott A Tomlins15, Cory Abate-Shen4, Nima Sharifi16, Owen N Witte17, Felix Y Feng18, Karen E Knudsen19.
Abstract
Emerging evidence demonstrates that the DNA repair kinase DNA-PKcs exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PKcs functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PKcs inhibits tumor metastases. Clinical assessment revealed that DNA-PKcs is significantly elevated in advanced disease and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PKcs in advanced tumors is highly activated, independent of DNA damage indicators. Combined, these findings reveal unexpected DNA-PKcs functions, identify DNA-PKcs as a potent driver of tumor progression and metastases, and nominate DNA-PKcs as a therapeutic target for advanced malignancies.Entities:
Mesh：
Substances：
Year: 2015 PMID： 26175416 PMCID： PMC4531387 DOI： 10.1016/j.ccell.2015.06.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743