Estrogen and ERα enhanced β‐catenin degradation and suppressed its downstream target genes to block the metastatic function of HA22T hepatocellular carcinoma cells via modulating GSK‐3β and β‐TrCP expression |
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| Authors: | Yu‐Feng Chen Bharath Kumar Velmurugan Hwai‐Lee Wang Chuan‐Chou Tu Ray‐Jade Che Ming‐Cheng Chen Long‐Bin Jen Vijaya Padma Vishwanadha Hsi‐Hsien Hsu Chih‐Yang Huang |
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| Affiliation: | 1. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;2. Section of Cardiology, Yuan Rung Hospital, Yuanlin, Taiwan;3. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan;4. Department of Internal Medicine, Division of Chest Medicine, Armed Force Taichung General Hospital, Taichung, Taiwan;5. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;6. Division of Colorectal Surgery, Veterans General Hospital, Taichung, Taiwan;7. Department of Surgery, China Medical University Hospital, Taichung, Taiwan;8. Department of Biotechnology, Bharathiar University, Coimbatore, India;9. Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan;10. Mackay Medicine, Nursing and Management College, Taipei, Taiwan;11. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan |
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| Abstract: | In our previous experiments, we found β‐catenin was highly expressed in the tumor area with high invasive ability and poor prognosis. In this study, we have examined the mechanism by which ERα regulates β‐catenin expression as well as the metastasis ability of hepatocellular cancer HA22T cells. To identify whether the anticancer effect of estrogen and ERα is mediated through suppression of β‐catenin expression, we co‐transfected pCMV‐β‐catenin and ERα into HA22T cells, and determined the cell motility by wound healing, invasion, and migration assays. Results showed that estrogen and/or ERα inhibited β‐catenin gene expression and repressed HA22T cell motility demonstrated that similar data was observed in cells expressing the ERα stable clone. Moreover, we examined the protein‐protein interaction between ERα and β‐catenin by immunostain, co‐immunoprecipitation, and Western blotting. E2 enhanced the binding of ERα with β‐catenin and then triggered β‐catenin to bind with E3 ligase (βTrCP) to promote β‐catenin degradation. Finally by employing systematic ChIP studies, we showed ERα can interact directly with the β‐catenin promoter region following E2 treatment. All our results reveal that estrogen and ERα blocked metastatic function of HA22T cells by modulating GSK3β and βTrCP expression and further enhanced β‐catenin degradation and suppressed its downstream target genes. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 519–529, 2017. |
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| Keywords: | β ‐catenin ERα metastasis GSK3β |
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