DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis.
Publication/Presentation Date
7-13-2015
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.
Volume
28
Issue
1
First Page
97
Last Page
113
ISSN
1878-3686
Published In/Presented At
Goodwin, J. F., Kothari, V., Drake, J. M., Zhao, S., Dylgjeri, E., Dean, J. L., Schiewer, M. J., McNair, C., Jones, J. K., Aytes, A., Magee, M. S., Snook, A. E., Zhu, Z., Den, R. B., Birbe, R. C., Gomella, L. G., Graham, N. A., Vashisht, A. A., Wohlschlegel, J. A., Graeber, T. G., … Knudsen, K. E. (2015). DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis. Cancer cell, 28(1), 97–113. https://doi.org/10.1016/j.ccell.2015.06.004
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
26175416
Department(s)
Administration and Leadership
Document Type
Article