Regulation of the Microenvironment by Rho GTPase Signaling in the Epithelium: Implications for Breast Cancer Development and Progression

Deregulation of Rho GTPase expression and activity levels is found in a number of cancers, including breast cancers. Aberrant Rho GTPase signaling promotes tumorigenic behaviors in a cell-autonomous manner. The development of conditional knockout and overexpression mouse models of Rho GTPases and their regulators has allowed for investigation of the impact of aberrant Rho signaling in the context of the complex in vivo environment. These studies, including studies from our laboratory investigating the effects of Cdc42 and p190B RhoGAP overexpression in the developing mammary gland, indicate that altered Rho signaling in the epithelium impacts the microenvironment. We propose that hyperactivated Rho signaling in neoplastic cells may contribute to tumor formation by promoting the development of a pro-tumorigenic and pro-invasive microenvironment. The availability of conditional Rho GTPase mouse models will facilitate these studies in the future.