- Main
DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis.
- Author(s): Goodwin, Jonathan F
- Kothari, Vishal
- Drake, Justin M
- Zhao, Shuang
- Dylgjeri, Emanuela
- Dean, Jeffry L
- Schiewer, Matthew J
- McNair, Christopher
- Jones, Jennifer K
- Aytes, Alvaro
- Magee, Michael S
- Snook, Adam E
- Zhu, Ziqi
- Den, Robert B
- Birbe, Ruth C
- Gomella, Leonard G
- Graham, Nicholas A
- Vashisht, Ajay A
- Wohlschlegel, James A
- Graeber, Thomas G
- Karnes, R Jeffrey
- Takhar, Mandeep
- Davicioni, Elai
- Tomlins, Scott A
- Abate-Shen, Cory
- Sharifi, Nima
- Witte, Owen N
- Feng, Felix Y
- Knudsen, Karen E
- et al.
Published Web Location
https://doi.org/10.1016/j.ccell.2015.06.004Abstract
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.
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