Cancer Management and Research (Oct 2019)

Genetic And Epigenetic Regulation Of E-Cadherin Signaling In Human Hepatocellular Carcinoma

  • Fan X,
  • Jin S,
  • Li Y,
  • Khadaroo PA,
  • Dai Y,
  • He L,
  • Zhou D,
  • Lin H

Journal volume & issue
Vol. Volume 11
pp. 8947 – 8963

Abstract

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Xiaoxiao Fan,1,* Shengxi Jin,1,2,* Yirun Li,1 Parikshit Asutosh Khadaroo,2,3 Yili Dai,1,2 Lifeng He,1 Daizhan Zhou,1 Hui Lin1 1Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia*These authors contributed equally to this workCorrespondence: Hui Lin; Daizhan ZhouDepartment of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, People’s Republic of ChinaTel +86-13738055489; +86-21-61569704Fax +86-571-86044817; +86-21-61569704Email [email protected]; [email protected]: E-cadherin is well known as a growth and invasion suppressor and belongs to the large cadherin family. Loss of E-cadherin is widely known as the hallmark of epithelial-to-mesenchymal transition (EMT) with the involvement of transcription factors such as Snail, Slug, Twist and Zeb1/2. Tumor cells undergoing EMT could migrate to distant sites and become metastases. Recently, numerous studies have revealed how the expression of E-cadherin is regulated by different kinds of genetic and epigenetic alteration, which are implicated in several crucial transcription factors and pathways. E-cadherin signaling plays an important role in hepatocellular carcinoma (HCC) initiation and progression considering the highly mutated frequency of CTNNB1 (27%). Combining the data from The Cancer Genome Atlas (TCGA) database and previous studies, we have summarized the roles of gene mutations, chromosome instability, DNA methylation, histone modifications and non-coding RNA in E-cadherin in HCC. In this review, we discuss the current understanding of the relationship between these modifications and HCC. Perspectives on E-cadherin-related research in HCC are provided.Keywords: E-cadherin, HCC, genetic alterations, epigenetic alterations

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