4314

MMP3

Lung cancer is more deadly than colon, breast, and prostate cancers combined, and treatment improvements have failed to improve prognosis significantly. Here, we identify a critical mediator of lung cancer progression, Rac1b, a tumor-associated protein with cell-transforming properties that are linked to the matrix metalloproteinase (MMP)-induced epithelial-mesenchymal transition (EMT) in lung epithelial cells. We show that expression of mouse Rac1b in lung epithelial cells of transgenic mice stimulated EMT and spontaneous tumor development and that activation of EMT by MMP-induced expression of Rac1b gave rise to lung adenocarcinoma in the transgenic mice through bypassing oncogene-induced senescence. Rac1b is expressed abundantly in stages 1 and 2 of human lung adenocarcinomas and, hence, is an attractive molecular target for the development of new therapies that prevent progression to later-stage lung cancers.

Ras homolog family member C (RHOC) is important during the progression of several types of cancer, including prostate, breast and hepatocellular carcinoma. However, the function of RHOC in cholangiocellular carcinoma (CCC), a highly recurrent and metastatic carcinoma with poor prognosis, remains unclear. The aim of the present study was to investigate the involvement of RHOC in CCC tumor progression. RHOC expression levels were examined in CCC tissues and cells, and adjacent nontumorous bile duct tissues. The effects and molecular mechanisms of RHOC expression on cell migration and invasion were also investigated. The current study demonstrated that RHOC protein was frequently overexpressed in human CCC specimens and CCC cell lines. Downregulation of RHOC inhibited CCC cell invasion and migration partially via inhibition of matrix metalloproteinase 2, 3 and 9 expression. RHOC also modulated the expression of several epithelial-mesenchymal transition (EMT)-associated proteins, including Ecadherin, vimentin, Slug and Snail, to promote to EMT progression. The present results demonstrated that RHOC is important for the invasion and migration of CCC through simultaneous regulation of MMPs and EMTassociated protein, suggesting that RHOC is a potential molecular target for CCC treatment.