title: Transforming growth factor-β1-induced epithelial-mesenchymal transition generates ALDH-positive cells with stem cell properties in cholangiocarcinoma.
abstract: 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-β1 (TGF-β1)-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-β1 and ALDH1 were correlated with poor prognosis in patients. We conclude that ALDH acts as a marker for CSCs in CCA, and TGF-β1-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.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, China; National Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Ze-Yu
authors.initials: ZY
authors.lastname: Shuang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, China; National Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, China; National Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, China; National Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Guohe
authors.initials: G
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, China; National Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Yong-Cheng
authors.initials: YC
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, China; National Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Lao
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, China; National Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; State Key Laboratory of Biocontrol, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, China; National Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China. Electronic address: lishp@sysucc.org.cn.
authors.forename: Shengping
authors.initials: S
authors.lastname: Li
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001650:Bile Duct Neoplasms / Q000201:enzymology / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000201:enzymology / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D053773:Transforming Growth Factor beta1; D000444:Aldehyde Dehydrogenase
keywords: Aldehyde dehydrogenase; Cancer stem cells; Cholangiocarcinoma; Epithelial–mesenchymal transition; Transforming growth factor-β1