The Rho subgroup of the Rho GTPases consisting of RhoA, RhoB and RhoC induces a 
specific type of actin cytoskeleton and carry out a variety of functions in the 
cell. mDia and ROCK are downstream effectors of Rho mediating Rho action on the 
actin cytoskeleton; mDia produces actin filaments by nucleation and 
polymerization and ROCK activate myosin to cross-link them for induction of 
actomyosin bundles and contractility. mDia is potentially linked to Rac 
activation and membrane ruffle formation through c-Src-induced phosphorylation 
of focal adhesion proteins, and ROCK antagonizes this mDia action. Thus, cell 
morphogenesis, adhesion, and motility can be determined by the balance between 
mDia and ROCK activities. Though they are not oncogenes by themselves, 
overexpression of RhoA and RhoC are often found in clinical cancers, and RhoC 
has been repeatedly identified as a gene associated with metastasis. The 
Rho-ROCK pathway is implicated in Ras-mediated transformation, the amoeboid 
movement of tumor cells in the three-dimensional matrix, and transmigration of 
tumor cells through the mesothelial monolayer. On the other hand, the Rho-mDia1 
pathway is implicated in Src-mediated remodeling of focal adhesions and 
migration of tumor cells. There is also an indication that the Rho pathway other 
than ROCK is involved in Src-mediated induction of podosome and regulation of 
matrix metalloproteases. Thus, Rho mediates various phenotypes of malignant 
transformation by Ras and Src through its effectors, ROCK and mDia.