ArticleCell death & disease2016
Chemotherapy resistance and metastasis-promoting effects of thyroid hormone in hepatocarcinoma cells are mediated by suppression of FoxO1 and Bim pathway.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Acetylated KIAA1429 by TIP60 facilitates metastasis and immune evasion of hepatocellular carcinoma via N6-methyladenosine-KDM5B-mediated regulation of FoxO1.Cell death discovery · 2025Article
- Acetylation of FOXO1 activates Bim expression involved in CVB3 induced cardiomyocyte apoptosis.Apoptosis : an international journal on programmed cell death · 2024Article
- FOXO1 represses MCL1 transcription to regulate the function of vascular smooth muscle cells in intracranial aneurysm.Experimental brain research · 2022Article
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- Screening of Hub Genes in Hepatocellular Carcinoma Based on Network Analysis and Machine Learning.Computational and mathematical methods in medicine · 2022Article
- Role of Forkhead Box O Proteins in Hepatocellular Carcinoma Biology and Progression (Review).Frontiers in oncology · 2021Review
- Anticancer Effects ofJournal of Cancer · 2021Article
- DOCK6 promotes chemo- and radioresistance of gastric cancer by modulating WNT/β-catenin signaling and cancer stem cell traits.Oncogene · 2020Article
- RCC2 contributes to tumor invasion and chemoresistance to cisplatin in hepatocellular carcinoma.Human cell · 2020Article
- Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1.The Journal of biological chemistry · 2020Article
- Article
- Knockdown of miR-183 Enhances the Cisplatin-Induced Apoptosis in Esophageal Cancer Through Increase of FOXO1 Expression.OncoTargets and therapy · 2020Article
- Establishment of a Prognostic Model Using Immune-Related Genes in Patients With Hepatocellular Carcinoma.Frontiers in genetics · 2020Article
- Thyroid Hormone in Hepatocellular Carcinoma: Cancer Risk, Growth Regulation, and Anticancer Drug Resistance.Frontiers in medicine · 2020Review
- FOXO1 overexpression is correlated with poor prognosis in epithelial ovarian cancer.Cancer biomarkers : section A of Disease markers · 2020Article
- Roles of Thyroid Hormone-Associated microRNAs Affecting Oxidative Stress in Human Hepatocellular Carcinoma.International journal of molecular sciences · 2019Review
- miR-374a Inhibitor Enhances Etoposide-Induced Cytotoxicity Against Glioma Cells Through Upregulation of FOXO1.Oncology research · 2019Article
- Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases.Journal of biomedical science · 2019Review
- Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS.International journal of molecular medicine · 2019Article
- Review
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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