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000127576 1001_ $$0P:(DE-HGF)0$$aStoy, Christian$$b0$$eFirst author
000127576 245__ $$aTranscriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy.
000127576 260__ $$aWeinheim$$bWiley-VCH$$c2015
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000127576 520__ $$aPancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here, we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI3 kinase signaling which in turn could rescue TBL1 deficiency-dependent phenotypes. TBL1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo. As TBL1 mRNA levels were also found to correlate with PI3 kinase levels and overall survival in a cohort of human PDAC patients, TBL1 was identified as a checkpoint in the malignant behavior of pancreatic cancer and its expression may serve as a novel molecular target in the treatment of human PDAC.
000127576 536__ $$0G:(DE-HGF)POF3-311$$a311 - Signalling pathways, cell and tumor biology (POF3-311)$$cPOF3-311$$fPOF III$$x0
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000127576 650_7 $$2NLM Chemicals$$aTBL1X protein, human
000127576 650_7 $$2NLM Chemicals$$aTbl1x protein, mouse
000127576 650_7 $$0EC 3.6.5.1$$2NLM Chemicals$$aTransducin
000127576 7001_ $$0P:(DE-He78)81661d885b9d708589e84a280d2796d4$$aSundaram, Aishwarya$$b1$$udkfz
000127576 7001_ $$0P:(DE-He78)34a94db0c76003e41d389cca7e4c0826$$aRios Garcia, Marcos$$b2$$udkfz
000127576 7001_ $$0P:(DE-HGF)0$$aWang, Xiaoyue$$b3
000127576 7001_ $$0P:(DE-HGF)0$$aSeibert, Oksana$$b4
000127576 7001_ $$0P:(DE-HGF)0$$aZota, Annika$$b5
000127576 7001_ $$0P:(DE-HGF)0$$aWendler, Susann$$b6
000127576 7001_ $$aMännle, David$$b7
000127576 7001_ $$aHinz, Ulf$$b8
000127576 7001_ $$aSticht, Carsten$$b9
000127576 7001_ $$aMuciek, Maria$$b10
000127576 7001_ $$aGretz, Norbert$$b11
000127576 7001_ $$aRose, Adam J$$b12
000127576 7001_ $$0P:(DE-HGF)0$$aGreiner, Vera$$b13
000127576 7001_ $$0P:(DE-He78)99ae95278bd95e30462a4fb2d12026c6$$aHofmann, Thomas$$b14$$udkfz
000127576 7001_ $$0P:(DE-He78)f8c334e84e585d7fa09d4d4b2d322041$$aBauer, Andrea$$b15$$udkfz
000127576 7001_ $$0P:(DE-He78)c684a26e52cc44716354a4d15f530b4e$$aHoheisel, Jörg$$b16$$udkfz
000127576 7001_ $$0P:(DE-HGF)0$$aBerriel Diaz, Mauricio$$b17
000127576 7001_ $$aGaida, Matthias M$$b18
000127576 7001_ $$aWerner, Jens$$b19
000127576 7001_ $$aSchafmeier, Tobias$$b20
000127576 7001_ $$0P:(DE-HGF)0$$aStrobel, Oliver$$b21
000127576 7001_ $$0P:(DE-He78)e527f794b23172e769c8904180546f57$$aHerzig, Stephan$$b22$$eLast author$$udkfz
000127576 773__ $$0PERI:(DE-600)2485479-7$$a10.15252/emmm.201404837$$gVol. 7, no. 8, p. 1048 - 1062$$n8$$p1048 - 1062$$tEMBO molecular medicine$$v7$$x1757-4684$$y2015
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