Journal
CANCER LETTERS
Volume 354, Issue 2, Pages 320-328Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.08.030
Keywords
Epithelial-mesenchymal transition; Cancer stem cells; Transforming growth factor-beta 1; Aldehyde dehydrogenase; Cholangiocarcinoma
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Funding
- Major National Scientific Research Projects of China [2013CB910304]
- National Natural Science Foundation of China [81171890]
- Guangdong Natural Science Foundation of China [S2011010004047]
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Epithelial-mesenchymal transition (EMT) is a major factor that facilitates the invasiveness and metastasis of cancer. Recent studies have demonstrated that EMT plays a key role in generating cancer stem cells (CSCs). This study aimed to investigate the effect of EMT on CSCs that were identified as positive for aldehyde dehydrogenase (ALDH) in cholangiocarcinoma (CCA). We demonstrated that transforming growth factor-beta 1 (TGF-beta 1)-induced EMT in the human cholangiocarcinoma (CCA) cell line, TFK-1, resulted in the acquisition of mesenchymal traits, as well as the expression of ALDH, which was accompanied by decreased sensitivity to the chemotherapeutic agent, 5-fluorouracil. ALDH-positive cells isolated from TFK-1 cells had higher proliferation potential in vitro and tumourigenic ability in vivo. They also expressed mesenchymal markers. Moreover, the expression levels of TGF-beta 1 and ALDH1 were correlated with poor prognosis in patients. We conclude that ALDH acts as a marker for CSCs in CCA, and TGF-beta 1-induced EMT is involved in the generation of CSCs. These findings offer a new tool for the study of CCA stem cells and illustrate a direct link between EMT and the gain of stem-cell properties. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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