Areview on notch, tgf- β and mapk signaling pathways in the progression of colorectal cancer

Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer death. A complex multistep process involves in Colorectal carcinogenesis, starts with progressivedisruption of intestinal epithelial-cell proliferation, apoptosis, differentiation and survival mechanisms. Since the disturbance in signaling pathways leads to cancer, then In this review, we will focus on someof the recent developments in the study of Notch, TGF-β and MAPK signaling pathway, as those relate to colorectal cancer susceptibility. Studies indicate that activation of Notch , TGF-β and MAPKsignaling are critically involved in several biological processes, including cell proliferation, differentiation and apoptosis. Many studies reported that Notch signaling has an oncogenic role in colorectal cancer and TGF-β signaling is one of the downstream pathway of notch signaling activation. Recently strong studies suggest some degrees of TGF-β signaling alterations which mediated by mutations or polymorphisms of TGF-β receptors or SMADs contribute to colon cancer development and progression. TGF-β signaling activates a series of non-Smad pathways, one of which is MAPK signaling. Involvement of various MAPK pathways have been reported to be linked with the processes o f oncogenesis. Essentially of ERK activation for cell-cycle entry and thus mitogenesis has been reported in asset of studies. So Notch-TGF-β,MAPK- ERK could be consider as a novel therapeutic pathway in colorectal cancer. Any breakdown in upstream of this pathway may lead to cancer breakthrough.

Keywords:

Colorectal Cancer , Cancer Prevention , Gene and Cancer , Cell and Cancer , Cancer Genetics