Tumor suppressor p53 restricts Ras stimulation of RhoA and cancer cell motility

Abstract

Many features of the cancer cell phenotype emerge as a result of cooperation between multiple oncogenic mutations. Here we show that activated Ras(V12) and loss of p53 function can cooperate to promote cell motility, a feature closely associated with cancer progression to malignancy. Our analysis indicates that Ras(V12) and loss of p53 synergistically induce RhoA activity, revealing a previously unknown role for p53 in tumor suppression. p53 prevents activation of RhoA and thus induction of cell motility by Ras(V12) through a simple signaling circuit, which integrates multiple inputs that converge on RhoA. Our data suggest that p53 suppresses cancer progression to malignancy by modulating the quality of Ras signaling.