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RB Loss Promotes Prostate Cancer Metastasis
Journal article   Open access   Peer reviewed

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, …
Cancer research (Chicago, Ill.), v 77(4), pp 982-995
15 Feb 2017
PMID: 27923835
url
https://doi.org/10.1158/0008-5472.can-16-1589View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Actins - metabolism Animals Cell Line, Tumor Cyclin-Dependent Kinase 4 - antagonists & inhibitors Cyclin-Dependent Kinase 6 - antagonists & inhibitors E2F Transcription Factors - physiology Extracellular Matrix Proteins - antagonists & inhibitors Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - physiology Humans Hyaluronan Receptors - genetics Hyaluronan Receptors - physiology Male Mice Neoplasm Metastasis Prostatic Neoplasms - pathology Retinoblastoma Protein - physiology rho-Associated Kinases - physiology Signal Transduction - physiology
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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Collaboration types
Domestic collaboration
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Web of Science research areas
Oncology
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