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Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3‐mediated down‐regulation of E‐cadherin
Author(s) -
Zhou Zhen,
Zhang HongSheng,
Liu Yang,
Zhang ZhongGuo,
Du GuangYuan,
Li Hu,
Yu XiaoYing,
Huang YingHui
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26012
Subject(s) - ezh2 , gene knockdown , ectopic expression , cancer research , chemistry , demethylase , epigenetics , cdh1 , histone h3 , carcinogenesis , epithelial–mesenchymal transition , histone , cadherin , microbiology and biotechnology , biology , metastasis , cell , cancer , apoptosis , gene , genetics , biochemistry
Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5‐hydroxymethylcytosine (5 hmC) by ten‐eleven translocation 1 (TET1) down‐regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial‐mesenchymal transition (EMT) and increased cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased EZH2 expression and reduced UTX‐1 expression, thus increasing histone H3K27 tri‐methylation causing repression of the target gene E‐cadherin. Ectopic expression of the H3K27 demethylase UTX‐1 or EZH2 depletion both impeded EZH2 binding caused a loss of H3K27 methylation at epithelial gene E‐cadherin promoter, thereby suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX‐1 depletion and ectopic expression of EZH2 enhanced EMT and tumor metastasis in DLD1 cells. These findings provide insight into the regulation of TET1 and E‐cadherin and identify EZH2 as a critical mediator of E‐cadherin repression and tumor progression.