Overexpression of RhoA enhances peritoneal dissemination: RhoA suppression with Lovastatin may be useful for ovarian cancer

The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion

“…These GTPases are monomeric 20-30 kDa GTPbinding proteins and function as molecular switches by altering between active GTP-bound and inactive GDPbound forms (Bar-Sagi and Hall, 2000). One of these Rho GTPases, RhoA, is upregulated in peritoneal metastatic lesions compared with primary tumors of advanced ovarian carcinoma (Dolo et al, 1995) and has an important role in the peritoneal dissemination of ovarian cancer cells (Horiuchi et al, 2008). RhoA has been known to regulate ovarian cancer cell migration and invasion through focal adhesion assembly (Sawada et al, 2002;Mukai et al, 2003).…”

The small GTPase RhoA regulates the expression and function of the sodium channel Nav1.5 in breast cancer cells

“…RhoA signaling pathways are implicated in the activation of FAK, Akt/PI3K, p38MAPK and MLCK, which have been shown to be responsible for cytoskeleton actin reorganization, cell adhesion, motility, migration and invasion (5)(6)(7)(8)(9). In many types of cancers, RhoA appears to be overexpressed and/or constitutively activated (10,11), and considered to be a negative clinical prognosis marker (10,12,13).…”

“…RhoA signaling pathways are implicated in the activation of FAK, Akt/PI3K, p38MAPK and MLCK, which have been shown to be responsible for cytoskeleton actin reorganization, cell adhesion, motility, migration and invasion (5-9). In many types of cancers, RhoA appears to be overexpressed and/or constitutively activated (10,11), and considered to be a negative clinical prognosis marker (10,12,13).Recently, it has been shown that the voltage-gated Na + channels (VGSCs) could be an accelerating factor in malignant cancers (14-17). VGSCs are membrane panning proteins expressed in a wide variety of excitable and non-excitable cells, as well as in many carcinomas including breast cancer (18,19).…”

RHOA (ras homolog gene family, member A)

“…Oncogenesis Expression of RhoA is significantly increased in advanced ovarian carcinomas and also in the peritoneal disseminated lesions (Horiuchi et al, 2008). The expression of the protein is further upregulated in tumors of stages III/IV when compared to those of stages I/II.…”