Rho family small GTPases

Rho family small GTPases – The Ras homologous (Rho) proteins also serve as key regulators of extracellular-stimulus-mediated signaling networks that regulate actin organization, cell cycle progression and gene expression. Twenty members have been identified, with RhoA, Rac1 and Cdc42 being the best studied. Rho GTPases are key regulators of actin reorganization. RhoA promotes actin stress fiber formation and focal adhesion assembly; Rac1 promotes lamellipodium formation and membrane ruffling; and Cdc42 promotes actin microspikes and filopodium formation. Consequently, Rho GTPases have been implicated in the regulation of cell polarity, cell movement, cell shape, and cell-cell and cell-matrix interactions, as well as in regulation of endocytosis and exocytosis.  Although Rho GTPases are not mutated in human cancers, their aberrant activation by indirect mechanisms contributes to cancer and other human diseases.  Our laboratory is elucidating mechanisms of aberrant Rho GTPase regulation in cancer.