ABCs of RhoGTPases indicating potential role as oncotargets

Abstract

RhoGTPases also known as molecular switches represent a family of GTP-binding proteins. They shuttle between "On" and "Off" states. In the "On" state, they activate plethora of molecules. These proteins perform a wide variety of functions involving cytoskeletal modeling, cell motility, migration, and mitosis. Members of this family are referred as master regulators of many cellular activities. Due to wide variety of portfolios attributed to RhoGTPases, their misbehavior leads to initiation and also progression of metastatic cancers. Many members of this family have been reported to be differentially regulated leading to spread of malignant cells from one site to other. These wandering cells find a comfortable site in accordance to Paget's soil and seed hypothesis and form secondary lesions. Out of multiple members of this family, RhoA and RhoC are important factors. RhoA is supposed to increase tumor proliferation when overexpressed while RhoC is responsible for tumor initiation. We searched publications on RhoGTPases, their functions and contribution in cancer development and metastasis on World Wide Web and PubMed. This review focuses on the role of Rac and Rho small GTPases in cell motility and granting the opportunistic motile behavior of aggressive cancer cells. To condense knowledge from existing literature about the roles played by these molecular switches, their structural and functional ramifications are introduced in the beginning followed by an account on their wrong behavior that leads to oncogenesis and oncoprogression. This piece of work highlights members of RhoGTPases as viable oncotargets.