RB loss promotes prostate cancer metastasis
Menée à l'aide de divers modèles murins de cancer de la prostate, cette étude met en évidence des mécanismes par lesquels la perte d'expression du gène RB favorise le processus métastatique
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 pro-metastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelia-mesenchyme translation, motility and invasion by cancer cells. Genetic modulation or pharmacological 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.