[PDF][PDF] DNA-PKcs-mediated transcriptional regulation drives prostate cancer progression and metastasis
Cancer cell, 2015•cell.com
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 …
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 …
Summary
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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