IMR Press / FBL / Volume 20 / Issue 6 / DOI: 10.2741/4349

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review
Epigenetic regulation of hepatic tumor-initiating cells
Jia Ding1,2Jian Wu1,3,4,*
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1 Key Laboratory of Medical Molecular Virology, Ministries of Education and Public Health, Fudan University Shanghai Medical College, Shanghai 200032, China
2 Department of Gastroenterology, Shanghai Jing’an District Central Hospital, Shanghai 200040, China
3 University of California, Davis Medical Center, Dept. of Internal Medicine, Division of Gastroenterology & Hepatology, Sacramento, CA 95817, USA
4 Shanghai Institute of Liver Diseases, Fudan University Affiliated Zhongshan Hospital, Shanghai 200032, China
Academic Editor:Wei Qin
Front. Biosci. (Landmark Ed) 2015, 20(6), 946–963; https://doi.org/10.2741/4349
Published: 1 June 2015
(This article belongs to the Special Issue Pathogenesis and diagnostic modalities in cancer)
Abstract

Hepatocellular carcinoma (HCC) is the third most lethal cancer and resistant to common chemotherapy. Tumor-initiating cells (T-ICs) that are thought to be responsible for tumorigenesis share surface markers and signaling pathways similar to normal tissue stem cells. Identification of T-ICs and elucidation of aberrant epigenetic modulation and self-renewal pathways may provide new insights into hepatic carcinogenesis, metastasis and chemotherapeutic resistance. Histone modification, DNA methylation and microenvironmental changes are considered as key elements to promote the derivation and function of T-ICs. In this review, we intend to compare the similarity and difference between normal liver stem cells and T-ICs, and to define the intrinsic and micro-environmental factors that lead to the transformation from normal liver stem cells to hepatic T-ICs. We believe that etiology, microenvironmental alteration, epigenetic modification and epithelial-mesenchymal transition play a fundamental role in initiating the transformation. Strategies targeting signaling molecules critical in modulating these processes may offer a personalized therapy for HCC in the future.

Keywords
Tumor-initiating cells
Cancer stem cells
Epigenetic regulation
Hepatocellular carcinoma
Review
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