TY  - JOUR
AU  - Stoy, Christian
AU  - Sundaram, Aishwarya
AU  - Rios Garcia, Marcos
AU  - Wang, Xiaoyue
AU  - Seibert, Oksana
AU  - Zota, Annika
AU  - Wendler, Susann
AU  - Männle, David
AU  - Hinz, Ulf
AU  - Sticht, Carsten
AU  - Muciek, Maria
AU  - Gretz, Norbert
AU  - Rose, Adam J
AU  - Greiner, Vera
AU  - Hofmann, Thomas
AU  - Bauer, Andrea
AU  - Hoheisel, Jörg
AU  - Berriel Diaz, Mauricio
AU  - Gaida, Matthias M
AU  - Werner, Jens
AU  - Schafmeier, Tobias
AU  - Strobel, Oliver
AU  - Herzig, Stephan
TI  - Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy.
JO  - EMBO molecular medicine
VL  - 7
IS  - 8
SN  - 1757-4684
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2017-03599
SP  - 1048 - 1062
PY  - 2015
AB  - Pancreatic 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.
KW  - TBL1X protein, human (NLM Chemicals)
KW  - Tbl1x protein, mouse (NLM Chemicals)
KW  - Transducin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26070712
C2  - pmc:PMC4551343
DO  - DOI:10.15252/emmm.201404837
UR  - https://inrepo02.dkfz.de/record/127576
ER  -