RB loss promotes prostate cancer metastasis

Chellappagounder Thangavel; Ettickan Boopathi; Yi Liu; Alex Haber; Adam Ertel; Anshul Bhardwaj; Sankar Addya; Noelle Williams; Stephen J. Ciment; Paolo Cotzia; Jeffry L. Dean; Adam Snook; Chris McNair; Matt Price; James R. Hernandez; Shuang G. Zhao; Ruth Birbe; James B. McCarthy; Eva A. Turley; Kenneth J. Pienta; Felix Y. Feng; Adam P. Dicker; Karen E. Knudsen; Robert B. Den

doi:10.1158/0008-5472.CAN-16-1589

RB loss promotes prostate cancer metastasis

Chellappagounder Thangavel, Ettickan Boopathi, Yi Liu, Alex Haber, Adam Ertel, Anshul Bhardwaj, Sankar Addya, Noelle Williams, Stephen J. Ciment, Paolo Cotzia, Jeffry L. Dean, Adam Snook, Chris McNair, Matt Price, James R. Hernandez, Shuang G. Zhao, Ruth Birbe, James B. McCarthy, Eva A. Turley, Kenneth J. PientaFelix Y. Feng, Adam P. Dicker, Karen E. Knudsen, Robert B. Den

School of Medicine

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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.

Original language	English (US)
Pages (from-to)	982-995
Number of pages	14
Journal	Cancer Research
Volume	77
Issue number	4
DOIs	https://doi.org/10.1158/0008-5472.CAN-16-1589
State	Published - Feb 15 2017

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-16-1589

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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., ... 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

Thangavel, C, Boopathi, E, Liu, Y, Haber, A, Ertel, A, Bhardwaj, A, Addya, S, Williams, N, Ciment, SJ, Cotzia, P, Dean, JL, Snook, A, McNair, C, Price, M, Hernandez, JR, Zhao, SG, Birbe, R, McCarthy, JB, Turley, EA, Pienta, KJ, Feng, FY, Dicker, AP, Knudsen, KE & Den, RB 2017, 'RB loss promotes prostate cancer metastasis', Cancer Research, vol. 77, no. 4, pp. 982-995. https://doi.org/10.1158/0008-5472.CAN-16-1589

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title = "RB loss promotes prostate cancer metastasis",

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.",

author = "Chellappagounder Thangavel and Ettickan Boopathi and Yi Liu and Alex Haber and Adam Ertel and Anshul Bhardwaj and Sankar Addya and Noelle Williams and Ciment, {Stephen J.} and Paolo Cotzia and Dean, {Jeffry L.} and Adam Snook and Chris McNair and Matt Price and Hernandez, {James R.} and Zhao, {Shuang G.} and Ruth Birbe and McCarthy, {James B.} and Turley, {Eva A.} and Pienta, {Kenneth J.} and Feng, {Felix Y.} and Dicker, {Adam P.} and Knudsen, {Karen E.} and Den, {Robert B.}",

note = "Publisher Copyright: {\textcopyright} 2016 American Association for Cancer Research.",

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doi = "10.1158/0008-5472.CAN-16-1589",

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AU - Thangavel, Chellappagounder

AU - Boopathi, Ettickan

AU - Liu, Yi

AU - Haber, Alex

AU - Ertel, Adam

AU - Bhardwaj, Anshul

AU - Addya, Sankar

AU - Williams, Noelle

AU - Ciment, Stephen J.

AU - Cotzia, Paolo

AU - Dean, Jeffry L.

AU - Snook, Adam

AU - McNair, Chris

AU - Price, Matt

AU - Hernandez, James R.

AU - Zhao, Shuang G.

AU - Birbe, Ruth

AU - McCarthy, James B.

AU - Turley, Eva A.

AU - Pienta, Kenneth J.

AU - Feng, Felix Y.

AU - Dicker, Adam P.

AU - Knudsen, Karen E.

AU - Den, Robert B.

PY - 2017/2/15

Y1 - 2017/2/15

N2 - 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.

AB - 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.

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RB loss promotes prostate cancer metastasis

Abstract

ASJC Scopus subject areas

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