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Epigenetic regulation of E-cadherin expression by the histone demethylase UTX in colon cancer cells

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Abstract

Decreased epithelial cadherin (E-cadherin) gene expression, a hallmark of epithelial–mesenchymal transition (EMT), is essential for triggering metastatic advantage of the colon cancer. Genetic mechanisms underlying the regulation of E-cadherin expression in EMT have been extensively investigated; however, much is unknown about the epigenetic mechanism underlying this process. Here, we identified ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase involved in demethylating di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), as a positive regulator for the expression of E-cadherin in the colon cancer cell line HCT-116. We showed that inactivation of UTX down-regulated E-cadherin gene expression, while overexpression of UTX did the opposite. Notably, overexpression of UTX inhibited migration and invasion of HCT-116 cells. Moreover, UTX demethylated H3K27me3, a histone transcriptional repressive mark, leading to decreased H3K27me3 at the E-cadherin promoter. Further, UTX interacted with the histone acetyltransferase (HAT) protein CBP and recruited it to the E-cadherin promoter, resulting in increased H3K27 acetylation (H3K27ac), a histone transcriptional active mark. UTX positively regulates E-cadherin expression through coordinated regulation of H3K27 demethylation and acetylation, switching the transcriptional repressive state to the transcriptional active state at the E-cadherin promoter. We conclude that UTX may play a role in regulation of E-cadherin gene expression in HCT-116 cells and that UTX may serve as a therapeutic target against the metastasis in the treatment of colon cancer.

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Acknowledgments

This study was supported by National Institutes of Health Grants (R01HL107500 to B.X., R01DK084172 to H.S.).

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Authors and Affiliations

  1. Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, China

    Lin Zha & Houjie Liang

  2. Department of Biology and Center for Obesity Reversal, Georgia State University, Atlanta, GA, 30303, USA

    Lin Zha, Qiang Cao, Xin Cui, Fenfen Li, Bingzhong Xue & Hang Shi

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  1. Lin Zha
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  3. Xin Cui
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Zha, L., Cao, Q., Cui, X. et al. Epigenetic regulation of E-cadherin expression by the histone demethylase UTX in colon cancer cells. Med Oncol 33, 21 (2016). https://doi.org/10.1007/s12032-016-0734-z

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