Pleiotropic Functions of Rho GTPase Signaling: A Trojan Horse or Achilles Heel for Breast Cancer Treatment?

P.R.      McHenry; T.      Vargo-Gogola

Abstract

Rho GTPase signaling is altered in human breast tumors, and elevated expression and activation of Rho GTPases correlate with tumor progression, metastasis, and poor prognosis. Here we review the evidence that Rho signaling functions as a key regulator of cell cycle, mitosis, apoptosis, and invasion during breast cancer growth and progression and discuss whether these pleiotropic actions enhance or limit the targetability of this network. We propose that depending on the stage and subtype of breast cancer, targeting Rho signaling may have chemopreventative, antitumor, and anti-metastatic efficacy. An understanding of how Rho signaling is perturbed in specific stages and subtypes of breast cancer and how it functions in the context of the complex in vivo environment during the stochastic process of tumor formation and progression are necessary in order to effectively target this signaling network for breast cancer treatment.

Keywords: Breast cancer, metastasis, Rho, GTPase, GEF, GAP, GDI, inhibitor, statins