RB Loss Promotes Prostate Cancer Metastasis.
Publication/Presentation Date
2-15-2017
Abstract
RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a prometastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelial-mesenchymal transition, motility, and invasion by cancer cells. Genetic modulation or pharmacologic inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer. Mechanistic studies in this setting established that RHAMM stabilized F-actin polymerization by controlling ROCK signaling. Collectively, our findings show how RB loss drives metastatic capacity and highlight RHAMM as a candidate therapeutic target for treating advanced prostate cancer.
Volume
77
Issue
4
First Page
982
Last Page
995
ISSN
1538-7445
Published In/Presented At
Thangavel, C., Boopathi, E., Liu, Y., Haber, A., Ertel, A., Bhardwaj, A., Addya, S., Williams, N., Ciment, S. J., Cotzia, P., Dean, J. L., Snook, A., McNair, C., Price, M., Hernandez, J. R., Zhao, S. G., Birbe, R., McCarthy, J. B., Turley, E. A., Pienta, K. J., … Den, R. B. (2017). RB Loss Promotes Prostate Cancer Metastasis. Cancer research, 77(4), 982–995. https://doi.org/10.1158/0008-5472.CAN-16-1589
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
27923835
Department(s)
Administration and Leadership
Document Type
Article