clinical-gastroentrology-2016_keynote

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Volume 6, Issue 6(Suppl) J Gastrointest Dig Syst
ISSN:2161-069X JGDS, an open access journal
Page 32
Clinical Gastroenterology 2016
October 03-05, 2016
conferenceseries.com
October 03-05, 2016 Toronto, Canada
8th International Conference on
Clinical Gastroenterology & Hepatology
Nathalie Rivard, J Gastrointest Dig Syst 2016, 6:6(Suppl)
The complex role of SHP-2 tyrosine phosphatase in the development of colorectal cancer
C olorectal cancer (CRC) is the third most common cancer in the world. A major risk factor to develop CRC is the presence
of chronic inflammation in the colon. But how chronic inflammation contributes to the development of CRC is not so
clear. In seeking to answer this question, we have focused on the signaling molecule SHP-2, a tyrosine phosphatase modulating
cellular signals induced by both growth factors and pro-inflammatory cytokines. Polymorphisms in the PTPN11 locus encoding
SHP-2 have been reported to be markers of colitis susceptibility. Conversely, gain-of-function mutations in PTPN11 have
recently been associated with sporadic CRC. To investigate the role of SHP-2 in intestinal homeostasis, we have generated mice
with an intestinal epithelial cell (IEC)-specific deletion of its expression. We demonstrated that IEC disruption of SHP-2 causes
severe chronic inflammation in the colon. This inflammatory phenotype is associated with a dramatic increase in proliferation
and activation of Wnt/β-catenin, NFkB and STAT3 signaling in colonic epithelium. With age, these mice develop malignant
lesions in the colon suggesting that SHP-2 can act as a tumor suppressor in this tissue. Furthermore, SHP-2 epithelial deficiency
severely increased colon tumor load in Apcmin/+ mice. Aside from these observations, we found increased expression and
activating mutations of SHP-2 in sporadic human colorectal tumors and SHP-2 silencing markedly attenuated KRAS-induced
transformation of IECs in culture. Hence, this suggests that SHP-2 can act as an oncogene in the colonic epithelium. Opposing
roles for SHP-2 in promoting and suppressing tumorigenesis in the large intestine are therefore proposed.
Biography
Nathalie Rivard has received her PhD from Université de Sherbrooke in 1994 and has completed her Post-doctorate at the Centre de Biochimie-CNRS, Université
de Nice, in France in 1997. She has worked as a Faculty Member in the Department of Anatomy and Cell Biology at the Faculté de Médecine et des Sciences de
la santé de l’Université de Sherbrooke. Her research focuses on the analysis of signaling pathways that control proliferation, differentiation, tumorigenesis and
inflammatory response of intestinal epithelial cells. She has published more than 80 papers in reputed journals. She is the recipient of 2013 Canadian Association
of Gastroenterology Research Excellence Award and holds a position of Canada Research Chair.
Nathalie Rivard
University of Sherbrooke, Canada