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@ARTICLE{Stoy:127576,
author = {C. Stoy$^*$ and A. Sundaram$^*$ and M. Rios Garcia$^*$ and
X. Wang$^*$ and O. Seibert$^*$ and A. Zota and S. Wendler
and D. Männle and U. Hinz and C. Sticht and M. Muciek and
N. Gretz and A. J. Rose and V. Greiner$^*$ and T.
Hofmann$^*$ and A. Bauer$^*$ and J. Hoheisel$^*$ and M.
Berriel Diaz and M. M. Gaida and J. Werner and T. Schafmeier
and O. Strobel and S. Herzig$^*$},
title = {{T}ranscriptional co-factor {T}ransducin beta-like ({TBL})
1 acts as a checkpoint in pancreatic cancer malignancy.},
journal = {EMBO molecular medicine},
volume = {7},
number = {8},
issn = {1757-4684},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {DKFZ-2017-03599},
pages = {1048 - 1062},
year = {2015},
abstract = {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.},
keywords = {TBL1X protein, human (NLM Chemicals) / Tbl1x protein, mouse
(NLM Chemicals) / Transducin (NLM Chemicals)},
cin = {A210 / B070 / A170},
ddc = {610},
cid = {I:(DE-He78)A210-20160331 / I:(DE-He78)B070-20160331 /
I:(DE-He78)A170-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26070712},
pmc = {pmc:PMC4551343},
doi = {10.15252/emmm.201404837},
url = {https://inrepo02.dkfz.de/record/127576},
}