title: Krüppel-like factor 8 promotes cancer stem cell-like traits in hepatocellular carcinoma through Wnt/β-catenin signaling.
abstract: Krüppel-like factor 8 (KLF8) is highly expressed in hepatocellular carcinoma (HCC) and contributes to tumor initiation and progression by promoting HCC cell proliferation and invasion. However, the role of KLF8 in liver cancer stem cells (LCSCs) is not known. In the current study, we investigated the role of KLF8 in LCSCs to determine if KLF8 is a novel marker of these cells. We found that KLF8 was highly expressed in primary HCC tumors, distant migrated tissues, and LCSCs. Patients with high KLF8 expression had a poor prognosis. KLF8 promoted stem cell-like features through activation of the Wnt/β-catenin signaling pathway. Cell apoptosis was significantly increased in HCC cells with knockdown of KLF8 compared with the control cells when treated with the same doses of sorafenib or cisplatin. Taken together, our study shows that KLF8 plays a potent oncogenic role in HCC tumorigenesis by maintaining stem cell-like features through activation of the Wnt/β-catenin signaling pathway and promoting chemoresistance. Thus, targeting KLF8 may provide an effective therapeutic approach to suppress tumorigenicity of HCC. © 2016 Wiley Periodicals, Inc.
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.|Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Shen
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hai-Guan
authors.initials: HG
authors.lastname: He
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: The 3rd Department of Surgery, The Third People's Hospital of Jiujiang, Jiujiang, Jiangxi Prov, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Yuan
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhou-Chong
authors.initials: ZC
authors.lastname: Wang
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Shi
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Xiangan Institute of Health of Retired Cadres, Second Military Medical University, Shanghai, China.
authors.forename: Yong-Peng
authors.initials: YP
authors.lastname: Wei
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Huang
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Guang-Shun
authors.initials: GS
authors.lastname: Yang
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D011379:Prognosis; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000077157:Sorafenib; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D000970:Antineoplastic Agents; C507402:KLF8 protein, human; D051741:Kruppel-Like Transcription Factors; D010671:Phenylurea Compounds; D012097:Repressor Proteins; D051153:Wnt Proteins; D009536:Niacinamide; D000077157:Sorafenib; D002945:Cisplatin
keywords: Krüppel-like factor 8 chemoresistance; hepatocellular carcinoma; liver cancer stem cells; prognosis