Previous Page  6 / 6
Information
Show Menu
Previous Page 6 / 6
Page Background

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

conference

series

.com

October 03-05, 2016 Toronto, Canada

8

th

International Conference on

Clinical Gastroenterology & Hepatology

Nathalie Rivard, J Gastrointest Dig Syst 2016, 6:6(Suppl)

http://dx.doi.org/10.4172/2161-069X.C1.039

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 Apc

min/+

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@usherbrooke.ca

Nathalie Rivard

University of Sherbrooke, Canada