SHP-2 phosphatase contributes to KRAS-driven intestinal oncogenesis but prevents colitis-associated cancer development.

ABSTRACT: A major risk factor of developing colorectal cancer (CRC) is the presence of chronic inflammation in the colon. In order to understand how inflammation contributes to CRC development, the present study focused on SHP-2, a tyrosine phosphatase encoded by PTPN11 gene in which polymorphisms have been shown to be markers of colitis susceptibility. Conversely, gain-of-function mutations in PTPN11 gene (E76 residue) have been found in certain sporadic CRC. Results shown herein demonstrate that SHP-2 expression was markedly increased in sporadic human adenomas but not in advanced colorectal tumors. SHP-2 silencing inhibited proliferative, invasive and tumoral properties of both intestinal epithelial cells (IECs) transformed by oncogenic KRAS and of human CRC cells. IEC-specific expression of a SH

SUBMITTER: Gagne-Sansfacon J 

PROVIDER: S-EPMC5323184 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature