Thyroid hormone receptors promote metastasis of human hepatoma cells via regulation of TRAIL

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题名:	Thyroid hormone receptors promote metastasis of human hepatoma cells via regulation of TRAIL
作者:	陳盛良;Chi, H-C;Chen, S-L;Liao, C-J;Liao, C-H;Tsai, M-M;Lin, Y-H;Huang, Y-H;Yeh, C-T;Wu, S-M;Tseng, Y-H;Chen, C-Y;Tsai, C-Y;Chung, I-H;Chen, W-J;Lin, K-H
贡献者:	生醫理工學院生命科學系
关键词:	631/80/82/23;631/80/86;692/420/755;692/699/67/1504/1610;Animals;Apoptosis;Apoptosis - drug effects;bcl-X Protein - antagonists & inhibitors;bcl-X Protein - genetics;bcl-X Protein - metabolism;Biochemistry;Biomedical and Life Sciences;Carcinoma, Hepatocellular - metabolism;Carcinoma, Hepatocellular - pathology;Cell adhesion & migration;Cell Biology;Cell Cycle Analysis;Cell death;Cell Line, Tumor;Genes;Hep G2 Cells;Humans;Kinases;Life Sciences;Ligands;Liver cancer;Liver Neoplasms - metabolism;Liver Neoplasms - pathology;Matrix Metalloproteinase 2 - metabolism;Matrix Metalloproteinase 7 - metabolism;Matrix Metalloproteinase 9 - metabolism;Metastasis;Mice;Mice, SCID;Neoplasm Metastasis;Original Paper;Proteins;Receptors, Thyroid Hormone - genetics;Receptors, Thyroid Hormone - metabolism;Stem Cells;Thyroid gland;TNF-Related Apoptosis-Inducing Ligand - genetics;TNF-Related Apoptosis-Inducing Ligand - metabolism;Transcription factors;Transplantation, Heterologous;Triiodothyronine - pharmacology;Tumor necrosis factor-TNF;Tumorigenesis;Up-Regulation - drug effects
日期:	2012-11-01
上传时间:	2026-04-23 11:14:06 (UTC+8)
出版者:	Nature Publishing Group;London: Nature Publishing Group UK
摘要:	摘要： Although accumulating evidence has confirmed the important roles of thyroid hormone (T 3 ) and its receptors (TRs) in tumor progression, the specific functions of TRs in carcinogenesis remain unclear. In the present study, tumor necrosis factor (TNF)-related apoptosis-inducing ligand ( TRAIL ) was directly upregulated by T 3 in TR-overexpressing hepatoma cell lines. TRAIL is an apoptotic inducer, but it can nonetheless trigger non-apoptotic signals favoring tumorigenesis in apoptosis-resistant cancer cells. We found that TR-overexpressing hepatoma cells treated with T 3 were apoptosis resistant, even when TRAIL was upregulated. This apoptotic resistance may be attributable to simultaneous upregulation of Bcl-xL by T 3 , because (1) knockdown of T 3 -induced Bcl-xL expression suppressed T 3 -mediated protection against apoptosis, and (2) overexpression of Bcl-xL further protected hepatoma cells from TRAIL-induced apoptotic death, consequently leading to TRAIL-promoted metastasis of hepatoma cells. Moreover, T 3 -enhanced metastasis in vivo was repressed by the treatment of TRAIL-blocking antibody. Notably, TRAIL was highly expressed in a subset of hepatocellular carcinoma (HCC) patients, and this high-level expression was significantly correlated with that of TRs in these HCC tissues. Together, our findings provide evidence for the existence of a novel mechanistic link between increased TR and TRAIL levels in HCC. Thus, TRs induce TRAIL expression, and TRAIL thus synthesized acts in concert with simultaneously synthesized Bcl-xL to promote metastasis, but not apoptosis. 其他題名： Cell Death Differ 出版者： London: Nature Publishing Group UK 出版日期： 2012-11-01 出處： Cell death and differentiation, 2012-11, Vol.19 (11), p.1802-1814 資源來源： EBSCOhost Academic Search Premier 版權： Macmillan Publishers Limited 2012 版權： Copyright Nature Publishing Group Nov 2012 版權： Copyright © 2012 Macmillan Publishers Limited 2012 Macmillan Publishers Limited 識別號： ISSN: 1350-9047 識別號： ISSN: 1476-5403 識別號： EISSN: 1476-5403 識別號： DOI: 10.1038/cdd.2012.58 識別號： PMID: 22576662
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