000203954 001__ 203954
000203954 005__ 20190317000052.0
000203954 0247_ $$2doi$$a10.1016/j.celrep.2014.08.041
000203954 022__ $$a2211-1247
000203954 02470 $$2ISI$$a000343867400033
000203954 037__ $$aARTICLE
000203954 245__ $$aPROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnt(high) Metastatic Colon Cancer Cells
000203954 269__ $$a2014
000203954 260__ $$bElsevier$$c2014$$aCambridge
000203954 300__ $$a17
000203954 336__ $$aJournal Articles
000203954 520__ $$aThe Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colorectal cancer cells is regulated by the target of oncogenic Wnt signaling, homeobox transcription factor PROX1, expressed by a subpopulation of colon cancer progenitor/stem cells. We identify direct PROX1 target genes and show that repression of a proapoptotic member of the BCL2 family, BCL2L15, is important for survival of PROX1(+) cells under metabolic stress. PROX1 inactivation after the establishment of metastases prevented further growth of lesions. Furthermore, autophagy inhibition efficiently targeted metastatic PROX1(+) cells, suggesting a potential therapeutic approach. These data identify PROX1 as a key regulator of the transcriptional network contributing to metastases outgrowth in colorectal cancer.
000203954 700__ $$uCHU Vaudois, Dept Oncol, CH-1066 Lausanne, Switzerland$$aRagusa, Simone
000203954 700__ $$uUniv Zurich, Instit Mol Canc Res, CH-8057 Zurich, Switzerland$$aCheng, Jianpin
000203954 700__ $$uCHU Vaudois, Dept Oncol, CH-1066 Lausanne, Switzerland$$aIvanov, Konstantin I.
000203954 700__ $$uSwiss Inst Bioinformat, SIB Bioinformat Core Facil, CH-1015 Lausanne, Switzerland$$aZangger, Nadine
000203954 700__ $$uCancer Res UK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland$$aCeteci, Fatih
000203954 700__ $$uCHU Vaudois, Dept Oncol, CH-1066 Lausanne, Switzerland$$aBernier-Latmani, Jeremiah
000203954 700__ $$uCHU Vaudois, Dept Oncol, CH-1066 Lausanne, Switzerland$$aMilatos, Stavros
000203954 700__ $$uCHU Vaudois, Serv Chirurg Pediat, CH-1011 Lausanne, Switzerland$$aJoseph, Jean-Marc
000203954 700__ $$uCHU Vaudois, Serv Chirurg Pediat, CH-1011 Lausanne, Switzerland$$aTercier, Stephane
000203954 700__ $$uUniv Lausanne, UNISciences, UniLabs, CH-1066 Lausanne, Switzerland$$aBouzourene, Hanifa
000203954 700__ $$uCHU Vaudois, Inst Univ Pathol, CH-1011 Lausanne, Switzerland$$aBosman, Fredrik T.
000203954 700__ $$uCHU Vaudois, Inst Univ Pathol, CH-1011 Lausanne, Switzerland$$aLetovanec, Igor
000203954 700__ $$uUniv Zurich, Instit Mol Canc Res, CH-8057 Zurich, Switzerland$$aMarra, Giancarlo
000203954 700__ $$uCHU Vaudois, Div Thorac Surg, CH-1011 Lausanne, Switzerland$$aGonzalez, Michel
000203954 700__ $$uCancer Res UK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland$$aCammareri, Patrizia
000203954 700__ $$uCancer Res UK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland$$aSansom, Owen J.
000203954 700__ $$uCHU Vaudois, Dept Oncol, CH-1066 Lausanne, Switzerland$$aDelorenzi, Mauro
000203954 700__ $$uCHU Vaudois, Dept Oncol, CH-1066 Lausanne, Switzerland$$aPetrova, Tatiana V.
000203954 773__ $$j8$$tCell Reports$$k6$$q1957-1973
000203954 8564_ $$uhttps://infoscience.epfl.ch/record/203954/files/1-s2.0-S2211124714007177-main.pdf$$zPublisher's version$$s8957885$$yPublisher's version
000203954 909C0 $$xU10454$$0252449$$pBMI
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000203954 917Z8 $$x182396
000203954 937__ $$aEPFL-ARTICLE-203954
000203954 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000203954 980__ $$aARTICLE