ArticleProceedings of the National Academy of Sciences of the United States of America2006
Activation of phosphatidylinositol 3-kinase signaling by a mutant thyroid hormone beta receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 148 citations in OpenAlex.
- Molecular Mechanisms of Thyroid Hormone Signaling in Thyroid Cancer: Oncogenesis, Progression, and Therapeutic Implications.Biomedicines · 2025Review
- Thyroid Hormone Action by Genomic and Nongenomic Molecular Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Carotenoids as modulators of the PI3K/Akt/mTOR pathway: innovative strategies in cancer therapy.Medical oncology (Northwood, London, England) · 2024Review
- Thyroid Hormone Receptors as Tumor Suppressors in Cancer.Endocrinology · 2024Review
- Understanding the Relationship between Nonalcoholic Fatty Liver Disease and Thyroid Disease.International journal of molecular sciences · 2023Review
- Pathogenesis of cancers derived from thyroid follicular cells.Nature reviews. Cancer · 2023Review
- Hyperthyroidism and Wnt Signaling Pathway: Influence on Bone Remodeling.Metabolites · 2023Review
- Thyroid receptor β might be responsible for breast cancer associated with Hashimoto's thyroiditis: a new insight into pathogenesis.Immunologic research · 2022Review
- Resistance to thyroid hormone beta coexisting with papillary thyroid carcinoma-two case reports of a thyroid hormone receptor beta gene mutation and a literature review.Frontiers in genetics · 2022Article
- Thyroid Hormone Receptor Beta Inhibits PI3K-Akt-mTOR Signaling Axis in Anaplastic Thyroid Cancer via Genomic Mechanisms.Journal of the Endocrine Society · 2021Article
- Akt isoform-specific effects on thyroid cancer development and progression in a murine thyroid cancer model.Scientific reports · 2020Article
- Coding Molecular Determinants of Thyroid Cancer Development and Progression.Endocrinology and metabolism clinics of North America · 2019Review
- Monocyte recruitment and activated inflammation are associated with thyroid carcinogenesis in a mouse model.American journal of cancer research · 2019Article
- Novel Transcriptional Mechanisms for Regulating Metabolism by Thyroid Hormone.International journal of molecular sciences · 2018Review
- Metformin and JQ1 synergistically inhibit obesity-activated thyroid cancer.Endocrine-related cancer · 2018Article
- Interplay between TRα1 and Wnt signaling: A dangerous liaison.Oncotarget · 2018Article
- PRL-3 promotes gastric cancer peritoneal metastasis via the PI3K/AKT signaling pathwayOncology letters · 2018Article
- Thyroid Hormone Receptor β Suppression of RUNX2 Is Mediated by Brahma-Related Gene 1-Dependent Chromatin Remodeling.Endocrinology · 2018Article
- Direct effects of thyroid hormones on hepatic lipid metabolism.Nature reviews. Endocrinology · 2018Review
- Review
29 more citing papers are in PubMed but not listed here.
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3 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B signaling pathway has been associated with multiple human cancers. Recently we showed that AKT is activated in both the thyroid and metastatic lesions of a mouse model of follicular thyroid carcinoma [thyroid hormone beta receptor (TRbeta)(PV/PV) mice]. This TRbeta(PV/PV) mouse harbors a knock-in mutant TRbeta gene (TRbetaPV mutant) that spontaneously develops thyroid cancer and distant metastasis similar to human follicular thyroid cancer. Here we show that in thyroid tumors, PV mutant bound significantly more to the PI3K-regulatory subunit p85alpha, resulting in a greater increase in the kinase activity than did TRbeta1 in wild-type mice. By GST pull-down assays, the ligand-binding domain of TR was identified as the interaction site with p85alpha. By confocal fluorescence microscopy, p85alpha was shown to colocalize with TRbeta1 or PV mainly in the nuclear compartment of cultured tumor cells from TRbeta(PV/PV) mice, but cytoplasmic p85alpha/PV or p85alpha/TRbeta1 complexes were also detectable. Further biochemical analysis revealed that the activation of the PI3K-AKT-mammalian target of the rapamycin-p70(S6K) pathway was observed in both the cytoplasmic and nuclear compartments, whereas the activation of the PI3K-integrin-linked kinase-matrix metalloproteinase 2 pathway was detected mainly in the extranuclear compartments. These results suggest that PV, via the activation of p85alpha, could act to affect PI3K downstream signaling in both the nuclear and extranuclear compartments, thereby contributing to thyroid carcinogenesis. Importantly, the present study unveils a mechanism by which a mutant TR acts to activate PI3K activity via protein-protein interactions.
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