Krüppel-like factor 8 promotes cancer stem cell-like traits in hepatocellular carcinoma through Wnt/β-catenin signaling

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• 作者：Yi-Nan Shen ; Hai-Guan He ; Yang Shi ; Jian Cao ; Jian-Yong Yuan ; Zhou-Chong Wang ; Chun-Feng Shi ; Nan Zhu ; Yong-Peng Wei ; Fang Liu ; Jia-Li Huang ; Guang-Shun Yang and Jun-Hua Lu
• 刊名：Molecular Carcinogenesis
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：56
• 期：2
• 页码：751-760
• 全文大小：1375K
• ISSN：1098-2744

文摘

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.