Journal
STEM CELL RESEARCH
Volume 17, Issue 2, Pages 367-378Publisher
ELSEVIER
DOI: 10.1016/j.scr.2016.08.007
Keywords
TBX3; Pancreas; Pancreatic adenocarcinoma; Development; Cancer stem cells
Funding
- Deutsche Forschungsgemeinschaft (DFG) [2544/1-1, 1-2]
- Forschungskern SyStaR
- BIU (Bohringer Ingelheim Ulm)
- Else-Kroner-Fresenius-Stiftung [2011_A200]
- German Cancer Aid Max Eder Fellowship
- German Cancer Aid Grant [111879]
- Fritz-Thyssen Foundation [2015-00363]
- Hector Foundation Cancer Research Fund
- Baden-Wurttemberg StiftungElite
- Interdisciplinary Center for Clinical Research (IZKF Aachen)
- RWTH Aachen University Medical School, Aachen, Germany
- Bausteinprogramm of Ulm University
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Cell fate decisions and pluripotency, but also malignancy depend on networks of key transcriptional regulators. The T-box transcription factor TBX3 has been implicated in the regulation of embryonic stem cell self-renewal and cardiogenesis. We have recently discovered that forced TBX3 expression in embryonic stem cells promotes mesendoderm specification directly by activating key lineage specification factors and indirectly by enhancing paracrine NODAL signalling. Interestingly, aberrant TBX3 expression is associated with breast cancer and melanoma formation. In other cancers, loss of TBX3 expression is associated with a more aggressive phenotype e.g. in gastric and cervical cancer. The precise function of TBX3 in pancreatic ductal adenocarcinoma remains to be determined. In the current study we provide conclusive evidence for TBX3 overexpression in pancreatic cancer samples as compared to healthy tissue. While proliferation remains unaltered, forced TBX3 expression strongly increases migration and invasion, but also angiogenesis in vitro and in vivo. Finally, we describe the TBX3-dependency of cancer stem cells that perpetuate themselves through an autocrine TBX3-ACTIVIN/NODAL signalling loop to sustain stemness. Thus, TBX3 is a new key player among pluripotency-related genes driving cancer formation. (C) 2016 The Authors. Published by Elsevier B.V.
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