Based on these observations other than non Smad signaling like RhoA GTPase and pERK1 2 pathways can be regulated by TGF beta, to induce the morphological changes observed in the Caco 2 trans formed and parental cells. Discussion blog of sinaling pathways BRAFV600E, KRASG12V and HRASG12V oncogenes Inhibitors,Modulators,Libraries differentially modify morphology and epithelial characteristics of Caco 2 cells As presented in this study, the three oncogenes induce different changes on cell morphology. Specifically, BRAFV600E alters the typical epithelial morphology of Caco 2 cells, the distribution of E cadherin and reduces Inhibitors,Modulators,Libraries its expression at the mRNA level. The elongated mor phology that Caco BR cells acquired lies between the epithelial of Caco 2 and the mesenchymal of HRASG12V transfected cells. However, the exact mechanism of this effect needs to be further inves tigated.

There is evidence that Rho GTPases play role in regulation of E cadherin. More specifically, active forms of Rac1 and Cdc42 have a positive effect on E cadherin mediated cell cell adhesions, while RhoA may also parti cipate to a lesser extent. On the other hand, KRASG12V does not alter the epithelial phenotype of the cells, but induces increased Inhibitors,Modulators,Libraries number of filopodia, actin rich finger like protrusions, that are important for cell polarity and the direction of cell movement. Regarding HRASG12V, EMT cells have an inva sive morphology, well illustrated both in 2D and 3D cell culture conditions and loss of E cadherin expression. It has been established that E cadherin expression can be downregulated in epithelial tumours by a number of mechanisms related to the induction of EMT.

In this study, BRAFV600E has provided Caco 2 cells with altered epithelial morphology and high migrating and invading capacity. High vimentin Inhibitors,Modulators,Libraries expression is not detected in Caco BR cells, like in Caco H with EMT characteristics. Instead, Caco BR cells over express another mesenchymal marker, N cadherin. Taken together these data suggest that BRAFV600E is able to relax cell cell junctions by reducing E cadherin expres sion and may drive Inhibitors,Modulators,Libraries colon epithelial cells to a more aggressive phenotype, while KRASG12V reserves their epithelial characteristics. The doubling time and the cell cycle distribution by means of flow cytometry for each oncogene has been already described. The increased proliferation rate of transformed cells may influence cell invasion, but this could not be the only reason for the enhanced invasive ability.

Here we show that small GTPase path ways regulate cell migration and invasion, which do not clearly affect cell proliferation pathways in our sys tem. More specifically, HRASG12V induces high prolif eration rates as well as very aggressive cell migration Dasatinib order and invasion properties associated with EMT pheno type. BRAFV600E provides maternal cells with increased proliferation and with enhanced migration properties.