Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3-mediated down-regulation of E-cadherin

Journal of Cellular Physiology
Zhen ZhouYing-Hui Huang

Abstract

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.

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Citations

Jan 20, 2018·International Journal of Molecular Sciences·Shau-Hsuan LiChang-Han Chen
Feb 28, 2019·Journal of Cellular and Molecular Medicine·Hong-Sheng ZhangYing-Hui Huang
Mar 27, 2019·Journal of Cellular Physiology·Shilong Ning, Xiao Ma
Oct 27, 2018·Journal of Cellular Physiology·Zhen ZhouYing-Hui Huang
Jan 11, 2020·Journal of Cellular and Molecular Medicine·Shenglong LiXiaojing Zhang
Jun 1, 2018·International Journal of Genomics·Chunyang FengTianmin Xu
Jun 2, 2018·International Journal of Cell Biology·Vincenzo GiancottiClaudio Rizzi
Feb 24, 2021·The Journal of Cell Biology·Roshan L ShresthaMunira A Basrai
Mar 27, 2020·Archives of Biochemistry and Biophysics·Hong-Liang SunHong-Sheng Zhang
Apr 30, 2021·Journal of Cancer Research and Clinical Oncology·Jyoti ShekhawatMithu Banerjee

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