Open AccessTranscriptional co‐factor Transducin beta‐like ( TBL ) 1 acts as a checkpoint in pancreatic cancer malignancy
Author(s) -
Stoy Christian,
Sundaram Aishwarya,
Rios Garcia Marcos,
Wang Xiaoyue,
Seibert Oksana,
Zota Annika,
Wendler Susann,
Männle David,
Hinz Ulf,
Sticht Carsten,
Muciek Maria,
Gretz Norbert,
Rose Adam J,
Greiner Vera,
Hofmann Thomas G.,
Bauer Andrea,
Hoheisel Jörg,
Berriel Diaz Mauricio,
Gaida Matthias M,
Werner Jens,
Schafmeier Tobias,
Strobel Oliver,
Herzig Stephan
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404837
Subject(s) - pancreatic cancer , malignancy , cancer research , cancer , chemistry , microbiology and biotechnology , medicine , biology , endocrinology
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 TBL 1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI 3 kinase signaling which in turn could rescue TBL 1 deficiency‐dependent phenotypes. TBL 1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI 3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo . As TBL 1 mRNA levels were also found to correlate with PI 3 kinase levels and overall survival in a cohort of human PDAC patients, TBL 1 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 .