Journal article
RB Loss Promotes Prostate Cancer Metastasis
Cancer research (Chicago, Ill.), v 77(4), pp 982-995
15 Feb 2017
PMID: 27923835
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- RB Loss Promotes Prostate Cancer Metastasis
- Creators
- Chellappagounder Thangavel - Thomas Jefferson UniversityEttickan Boopathi - Kimmel Cancer CenterYi Liu - Thomas Jefferson UniversityAlex Haber - Thomas Jefferson UniversityAdam Ertel - Sidney Kimmel Cancer CenterAnshul Bhardwaj - Thomas Jefferson UniversitySankar Addya - Kimmel Cancer CenterNoelle Williams - Thomas Jefferson UniversityStephen J Ciment - Thomas Jefferson UniversityPaolo Cotzia - Thomas Jefferson UniversityJeffry L Dean - Thomas Jefferson UniversityAdam Snook - Thomas Jefferson UniversityChris McNair - Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PennsylvaniaMatt Price - Department of Laboratory of Medicine and Pathology, University of Minnesota Masonic Cancer Center, Minneapolis, MinnesotaJames R Hernandez - Johns Hopkins UniversityShuang G Zhao - University of Michigan–Ann ArborRuth Birbe - Thomas Jefferson UniversityJames B McCarthy - University of MinnesotaEva A Turley - London Health Sciences CentreKenneth J Pienta - Johns Hopkins UniversityFelix Y Feng - University of Michigan–Ann ArborAdam P Dicker - Kimmel Cancer CenterKaren E Knudsen - Thomas Jefferson UniversityRobert B Den - Thomas Jefferson University
- Publication Details
- Cancer research (Chicago, Ill.), v 77(4), pp 982-995
- Publisher
- American Association for Cancer Research (AACR)
- Grant note
- R01 CA099996 / NCI NIH HHS P30 CA056036 / NCI NIH HHS R01 CA176401 / NCI NIH HHS R01 DK100483 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000393887800018
- Scopus ID
- 2-s2.0-85014128453
- Other Identifier
- 991019176806204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology