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

Cell Death and Differentiation
H-C ChiK-H Lin

Abstract

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 signif...Continue Reading

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Citations

Jun 5, 2010·Chemical & Pharmaceutical Bulletin·Hari Prasad DevkotaShoji Yahara
Jul 24, 2013·BioMed Research International·Hsiang Cheng ChiKwang-Huei Lin
Jul 18, 2014·Archivum Immunologiae Et Therapiae Experimentalis·Ammad Ahmad FarooqiHsueh-Wei Chang
Sep 8, 2012·Cellular and Molecular Life Sciences : CMLS·Sheng-Ming WuKwang-Huei Lin
Feb 23, 2013·Biochimica Et Biophysica Acta·Cheng-Yi ChenKwang-Huei Lin
Sep 13, 2015·Seizure : the Journal of the British Epilepsy Association·Seyedeh Masoumeh Seyedhoseini TamijaniAbolhassan Ahmadiani
Jul 24, 2013·Journal of Gastroenterology and Hepatology·Hongyang Wang, Lei Chen
Jan 27, 2015·Journal of Hepatology·Yang-Hsiang LinKwang-Huei Lin
Sep 21, 2017·Endocrine-related Cancer·Iuri Martin GoemannAna Luiza Maia
Aug 5, 2017·PloS One·Matthias PinterWolfgang Sieghart
Aug 14, 2018·Current Drug Targets·Duraiswamy BasavanMohan K S Kumar
Mar 29, 2019·Science Translational Medicine·Xingshen SunJohn F Engelhardt
Jun 5, 2015·Oncotarget·Hung-Yun LinPaul J Davis
Nov 27, 2019·International Journal of Molecular Sciences·Kam-Fai LeeKwang-Huei Lin
Mar 10, 2019·Journal of Biomedical Science·Hsiang-Cheng ChiKwang-Huei Lin
Feb 28, 2013·Cancer Research·Ya-Hui HuangKwang-Huei Lin

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