Details

Autor(en) / Beteiligte

• Zhou, Zhen
• Zhang, Hong‐Sheng
• Liu, Yang
• Zhang, Zhong‐Guo
• Du, Guang‐Yuan
• Li, Hu
• Yu, Xiao‐Ying
• Huang, Ying‐Hui

Titel

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

Ist Teil von

• Journal of cellular physiology, 2018-02, Vol.233 (2), p.1359-1369

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2018

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. TET1 depletion promoted cancer cell proliferation, migration, and invasion in DLD1 cells. TET1 depletion induced epithelial‐mesenchymal transition (EMT) in DLD1 cells. Modulation of H3K27me3 as a result of TET1 knockdown promotes DLD1 cancer cell migration.