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| 題名: | Chemotherapy resistance and metastasis-promoting effects of thyroid hormone in hepatocarcinoma cells are mediated by suppression of FoxO1 and Bim pathway |
| 作者: | 陳盛良;Chi, Hsiang-Cheng;Chen, Shen-Liang;Cheng, Yi-Hung;Lin, Tzu-Kang;Tsai, Chung-Ying;Tsai, Ming-Ming;Lin, Yang-Hsiang;Huang, Ya-Hui;Lin, Kwang-Huei |
| 貢獻者: | 生醫理工學院生命科學系 |
| 關鍵詞: | 13/2;13/89;38/109;42;42/109;42/35;631/45/776/1180;631/80/82/23;64/60;692/4020/4021/1607/1610/4029;692/699/67/1059/2326;Animals;Antibodies;Apoptosis - drug effects;Base Sequence;Bcl-2-Like Protein 11 - genetics;Bcl-2-Like Protein 11 - metabolism;Biochemistry;Biomedical and Life Sciences;Carcinoma, Hepatocellular - genetics;Carcinoma, Hepatocellular - pathology;Cell adhesion & migration;Cell Biology;Cell Culture;Chemotherapy;Cisplatin - pharmacology;Down-Regulation - drug effects;Doxorubicin - pharmacology;Drug Resistance, Neoplasm - drug effects;Forkhead Box Protein O1 - metabolism;Gene Expression Regulation, Neoplastic - drug effects;Hep G2 Cells;Hormones;Humans;Immunology;Life Sciences;Liver cancer;Liver Neoplasms - genetics;Liver Neoplasms - pathology;Metastasis;Mice, Inbred BALB C;Mice, Nude;Neoplasm Metastasis;Original;original-article;Promoter Regions, Genetic - genetics;Receptors, Thyroid Hormone - metabolism;RNA, Messenger - genetics;RNA, Messenger - metabolism;Signal transduction;Signal Transduction - drug effects;Thyroid Hormones - pharmacology;TNF-Related Apoptosis-Inducing Ligand - pharmacology |
| 日期: | 2016-08-04 |
| 上傳時間: | 2026-04-23 11:12:05 (UTC+8) |
| 出版者: | Nature Publishing Group;London: Nature Publishing Group UK |
| 摘要: | 摘要： Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, and systemic chemotherapy is the major treatment strategy for late-stage HCC patients. Poor prognosis following chemotherapy is the general outcome owing to recurrent resistance. Recent studies have suggested that in addition to cytotoxic effects on tumor cells, chemotherapy can induce an alternative cascade that supports tumor growth and metastasis. In the present investigation, we showed that thyroid hormone (TH), a potent hormone-mediating cellular differentiation and metabolism, acts as an antiapoptosis factor upon challenge of thyroid hormone receptor (TR)-expressing HCC cells with cancer therapy drugs, including cisplatin, doxorubicin and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TH/TR signaling promoted chemotherapy resistance through negatively regulating the pro-apoptotic protein, Bim, resulting in doxorubicin-induced metastasis of chemotherapy-resistant HCC cells. Ectopic expression of Bim in hepatoma cells challenged with chemotherapeutic drugs abolished TH/TR-triggered apoptosis resistance and metastasis. Furthermore, Bim expression was directly transactivated by Forkhead box protein O1 (FoxO1), which was negatively regulated by TH/TR. TH/TR suppressed FoxO1 activity through both transcriptional downregulation and nuclear exclusion of FoxO1 triggered by Akt-mediated phosphorylation. Ectopic expression of the constitutively active FoxO1 mutant, FoxO1-AAA, but not FoxO1-wt, diminished the suppressive effect of TH/TR on Bim . Our findings collectively suggest that expression of Bim is mediated by FoxO1 and indirectly downregulated by TH/TR, leading to chemotherapy resistance and doxorubicin-promoted metastasis of hepatoma cells.
其他題名： Cell Death Dis
出版者： London: Nature Publishing Group UK
出版日期： 2016-08-04
出處： Cell death & disease, 2016-08, Vol.7 (8), p.e2324-e2324
資源來源： Publicly Available Content Database
版權： The Author(s) 2016
版權： Copyright Nature Publishing Group Aug 2016
版權： Copyright © 2016 The Author(s) 2016 The Author(s)
識別號： ISSN: 2041-4889
識別號： EISSN: 2041-4889
識別號： DOI: 10.1038/cddis.2016.227
識別號： PMID: 27490929 |
| 顯示於類別: | [生命科學系] 期刊論文
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