000174960 001__ 174960
000174960 005__ 20180913061132.0
000174960 0247_ $$2doi$$a10.1038/onc.2011.218
000174960 02470 $$2ISI$$a000299176200005
000174960 037__ $$aARTICLE
000174960 245__ $$aIdentification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells
000174960 269__ $$a2012
000174960 260__ $$c2012
000174960 336__ $$aJournal Articles
000174960 520__ $$aCyclooxyganase-2 (COX-2), a rate-limiting enzyme in the prostaglandin synthesis pathway, is overexpressed in many cancers and contributes to cancer progression through tumor cell-autonomous and paracrine effects. Regular use of non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors (COXIBs) reduces the risk of cancer development and progression, in particular of the colon. The COXIB celecoxib is approved for adjunct therapy in patients with Familial adenomatous polyposis at high risk for colorectal cancer (CRC) formation. Long-term use of COXIBs, however, is associated with potentially severe cardiovascular complications, which hampers their broader use as preventive anticancer agents. In an effort to better understand the tumor-suppressive mechanisms of COXIBs, we identified MAGUK with Inverted domain structure-1 (MAGI1), a scaffolding protein implicated in the stabilization of adherens junctions, as a gene upregulated by COXIB in CRC cells and acting as tumor suppressor. Overexpression of MAGI1 in CRC cell lines SW480 and HCT116 induced an epithelial-like morphology; stabilized E-cadherin and beta-catenin localization at cell-cell junctions; enhanced actin stress fiber and focal adhesion formation; increased cell adhesion to matrix proteins and suppressed Wnt signaling, anchorage-independent growth, migration and invasion in vitro. Conversely, MAGI1 silencing decreased E-cadherin and beta-catenin localization at cell-cell junctions; disrupted actin stress fiber and focal adhesion formation; and enhanced Wnt signaling, anchorage-independent growth, migration and invasion in vitro. MAGI1 overexpression suppressed SW480 and HCT116 subcutaneous primary tumor growth, attenuated primary tumor growth and spontaneous lung metastasis in an orthotopic model of CRC, and decreased the number and size of metastatic nodules in an experimental model of lung metastasis. Collectively, these results identify MAG1 as a COXIB-induced inhibitor of the Wnt/beta-catenin signaling pathway, with tumor-suppressive and anti-metastatic activity in experimental colon cancer. Oncogene (2012) 31, 48-59; doi: 10.1038/onc.2011.218; published online 13 June 2011
000174960 6531_ $$aCox-2
000174960 6531_ $$aWnt signaling
000174960 6531_ $$ametastasis
000174960 6531_ $$acolorectal cancer
000174960 6531_ $$atumor suppressor
000174960 6531_ $$aNonsteroidal Antiinflammatory Drugs
000174960 6531_ $$aFamilial Adenomatous Polyposis
000174960 6531_ $$aIntegrin-Mediated Adhesion
000174960 6531_ $$aColon-Cancer
000174960 6531_ $$aGuanylate Kinase
000174960 6531_ $$aEpithelial-Cells
000174960 6531_ $$aScaffolding Molecule
000174960 6531_ $$aTissue Polarity
000174960 6531_ $$aTight Junctions
000174960 6531_ $$aBeta-Catenin
000174960 700__ $$aZaric, J.$$uUniv Fribourg UNIFR, Dept Med, Fac Sci, CH-1700 Fribourg, Switzerland
000174960 700__ $$aJoseph, J-M$$uUniv Lausanne UNIL, Univ Med Ctr CHUV, Dept Pediat Surg, Lausanne, Switzerland
000174960 700__ $$aTercier, S.$$uUniv Lausanne UNIL, Univ Med Ctr CHUV, Dept Pediat Surg, Lausanne, Switzerland
000174960 700__ $$aSengstag, T.$$uSwiss Inst Bioinformat SIB, Lausanne, Switzerland
000174960 700__ $$aPonsonnet, L.$$uUniv Lausanne UNIL, Univ Med Ctr CHUV, Multidisciplinary Oncol Ctr CePO, Div Expt Oncol, Lausanne, Switzerland
000174960 700__ $$aDelorenzi, M.$$uEcole Polytech Fed Lausanne EPFL, Swiss Inst Expt Canc Res ISREC, Natl Ctr Competence Res NCCR, Lausanne, Switzerland
000174960 700__ $$aRueegg, C.$$uUniv Fribourg UNIFR, Dept Med, Fac Sci, CH-1700 Fribourg, Switzerland
000174960 773__ $$j31$$q48-59$$tOncogene
000174960 909C0 $$0252450$$pISREC$$xU11153
000174960 909CO $$ooai:infoscience.tind.io:174960$$pSV$$particle
000174960 937__ $$aEPFL-ARTICLE-174960
000174960 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000174960 980__ $$aARTICLE