000216485 001__ 216485
000216485 005__ 20181203024152.0
000216485 0247_ $$2doi$$a10.1016/j.ebiom.2015.10.030
000216485 022__ $$a2352-3964
000216485 02470 $$2ISI$$a000367538100026
000216485 037__ $$aARTICLE
000216485 245__ $$aCL9/9L-beta-catenin Signaling is Associated With Poor Outcome in Colorectal Cancer
000216485 260__ $$bElsevier Science Bv$$c2015$$aAmsterdam
000216485 269__ $$a2015
000216485 300__ $$a12
000216485 336__ $$aJournal Articles
000216485 520__ $$aBCL9/9L proteins enhance the transcriptional output of the beta-catenin/TCF transcriptional complex and contribute critically to upholding the high WNT signaling level required for stemness maintenance in the intestinal epithelium. Here we show that a BCL9/9L-dependent gene signature derived from independent mouse colorectal cancer (CRC) models unprecedentedly separates patient subgroups with regard to progression free and overall survival. We found that this effect was by and large attributable to stemness related gene sets. Remarkably, this signature proved associated with recently described poor prognosis CRC subtypes exhibiting high stemness and/or epithelial-to-mesenchymal transition (EMT) traits. Consistentwith the notion that high WNT signaling is required for stemnessmaintenance, ablating Bcl9/9l-beta-catenin inmurine oncogenic intestinal organoids provoked their differentiation and completely abrogated their tumorigenicity, while not affecting their proliferation. Therapeutic strategies aimed at targetingWNT responses may be limited by intestinal toxicity. Our findings suggest that attenuating WNT signaling to an extent that affects stemness maintenance without disturbing intestinal renewal might be well tolerated and prove sufficient to reduce CRC recurrence and dramatically improve disease outcome. (C) 2015 The Authors. Published by Elsevier B.V.
000216485 6531_ $$aWNT signaling
000216485 6531_ $$aBCL9/9L-beta-catenin
000216485 6531_ $$aCancer stem cells
000216485 6531_ $$aColorectal cancer subtypes
000216485 6531_ $$aPatient outcome
000216485 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, ISREC, CH-1015 Lausanne, Switzerland$$aMoor, Andreas E.
000216485 700__ $$uUniv Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland$$aAnderle, Pascale
000216485 700__ $$uUniv Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland$$aCantu, Claudio
000216485 700__ $$0245204$$g209458$$uEcole Polytech Fed Lausanne, Sch Life Sci, ISREC, CH-1015 Lausanne, Switzerland$$aRodriguez, Patrick
000216485 700__ $$0243174$$g176894$$uEcole Polytech Fed Lausanne, Sch Life Sci, ISREC, CH-1015 Lausanne, Switzerland$$aWiedemann, Norbert
000216485 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, ISREC, CH-1015 Lausanne, Switzerland$$aBaruthio, Frederique
000216485 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, ISREC, CH-1015 Lausanne, Switzerland$$aDeka, Juergen
000216485 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, ISREC, CH-1015 Lausanne, Switzerland$$aAndre, Sylvie
000216485 700__ $$uUniv Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland$$aValenta, Tomas
000216485 700__ $$uUniv Lausanne, Dept Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland$$aMoor, Matthias B.
000216485 700__ $$uSemmelweis Univ, Dept Pediat 2, MTA TTK Lendulet Canc Biomarker Res Grp, H-1085 Budapest, Hungary$$aGyorffy, Balazs
000216485 700__ $$uSIB, CH-1015 Lausanne, Switzerland$$aBarras, David
000216485 700__ $$uSIB, CH-1015 Lausanne, Switzerland$$aDelorenzi, Mauro
000216485 700__ $$uUniv Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland$$aBasler, Konrad
000216485 700__ $$aAguet, Michel$$uEcole Polytech Fed Lausanne, Sch Life Sci, ISREC, CH-1015 Lausanne, Switzerland$$g168669$$0240585
000216485 773__ $$j2$$tEbiomedicine$$k12$$q1932-1943
000216485 909C0 $$xU11156$$0252150$$pUPAGU
000216485 909CO $$pSV$$particle$$ooai:infoscience.tind.io:216485
000216485 917Z8 $$x168669
000216485 917Z8 $$x168669
000216485 937__ $$aEPFL-ARTICLE-216485
000216485 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000216485 980__ $$aARTICLE