Involvement of Rho proteins at different stages of tumor progression. A) Maintenance of normal epithelial cell polarity. B) Benign tumors: once a tumor is initiated, Rho proteins can contribute to tumor development by stimulating dedifferentiation, growth and loss of cell polarity. C) Locally invasive tumors: Rho proteins can contribute to tumor development by altering cell-cell and cell-matrix adhesion, Rho proteins allow tumor cells to become invasive. D) Metastasis to distant site: Rho and ROCK are required for tumor cells to cross endothelial cell layers. RhoC promotes expression of angiogenic factors, leading to an increase in vascularization of the tumor.