Journal Article

DKFZ-2017-03599

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy.

Stoy, C. (First author)DKFZ* ; Sundaram, A.DKFZ* ; Rios Garcia, M.DKFZ* ; Wang, X.DKFZ* ; Seibert, O.DKFZ* ; Zota, A. ; Wendler, S. ; Männle, D. ; Hinz, U. ; Sticht, C. ; Muciek, M. ; Gretz, N. ; Rose, A. J. ; Greiner, V.DKFZ* ; Hofmann, T.DKFZ* ; Bauer, A.DKFZ* ; Hoheisel, J.DKFZ* ; Berriel Diaz, M. ; Gaida, M. M. ; Werner, J. ; Schafmeier, T. ; Strobel, O. ; Herzig, S. (Last author)DKFZ*

2015
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.15252/emmm.201404837

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.

Keyword(s): TBL1X protein, human ; Tbl1x protein, mouse ; Transducin

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Contributing Institute(s):

1. Zelluläre Seneszenz (A210)
2. Funktionelle Genomanalyse (B070)
3. Molekulare Stoffwechselkontrolle (A170)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2015

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Database coverage:
; ; ; BIOSIS Previews ; DOAJ Seal ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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