| Literature DB >> 27923835 |
Chellappagounder Thangavel1, Ettickan Boopathi2, Yi Liu1, Alex Haber1, Adam Ertel3,4, Anshul Bhardwaj5, Sankar Addya3,4, Noelle Williams1, Stephen J Ciment1, Paolo Cotzia6, Jeffry L Dean7, Adam Snook8, Chris McNair7, Matt Price9, James R Hernandez10, Shuang G Zhao11, Ruth Birbe6, James B McCarthy9, Eva A Turley12, Kenneth J Pienta10, Felix Y Feng11, Adam P Dicker1,4, Karen E Knudsen1,4,7,13, Robert B Den14,4,7,13.
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. Cancer Res; 77(4); 982-95. ©2016 AACR. ©2016 American Association for Cancer Research.Entities:
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Year: 2016 PMID： 27923835 PMCID： PMC5700768 DOI： 10.1158/0008-5472.CAN-16-1589
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701