Krüppel-like Factor 4 Blocks Hepatocellular Carcinoma Dedifferentiation and Progression through Activation of Hepatocyte Nuclear Factor-6

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Hongcheng SunKeping Xie

Abstract

Tumor differentiation is a behavioral index for hepatocellular carcinoma (HCC) and a prognostic factor for patients with HCC who undergo orthotopic liver transplantation (OLT). However, the molecular basis for HCC differentiation and prognostic value of the underlying molecules that regulate HCC differentiation are unclear. In this study, we defined a potential driver pathway for HCC differentiation and prognostication. The regulation and function of Krüppel-like factor 4 (KLF4) and hepatocyte nuclear factor-6 (HNF-6) in HCC differentiation was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival. There was a direct relationship between the expression levels of KLF4 and HNF6 in HCC. Reduced KLF4 or HNF6 expression correlated with high HCC grade. Poorly differentiated HCC cells had lower expression of KLF4 or HNF6 and differentiation-associated markers than did well-differentiated cells. Elevated KLF4 of HNF6 expression induced differentiation of poorly differentiated hepatoma cells. Mechanistically, KLF4 trans-activated HNF-6 expression. Restored HNF-6 expression upregulated expression of differentiation-associate...Continue Reading

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Citations

Mar 11, 2017·Leukemia & Lymphoma·Xin-Yu LiXin Wang
Apr 4, 2017·Gastroenterology·Chang-Kyung KimVincent W Yang
May 12, 2019·Expert Opinion on Therapeutic Targets·Evans D PopeKabir Mody
Mar 3, 2020·Microscopy Research and Technique·Kalsoom BashirMehrina Asghar
Oct 12, 2019·World Journal of Gastroenterology : WJG·Jia-Shuo ChaoHong-Cheng Sun
Dec 29, 2016·The Journal of Biological Chemistry·Qiaojiajie ZhaoDeng Chen
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Attila Becskei
Jan 26, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fanyang KongKeping Xie
Jun 12, 2021·Journal of Cellular and Molecular Medicine·Heeyoung YangTamina Park

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