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Published on: August 23, 2019
Thyroid Hormone Receptors as Tumor Suppressors in Cancer
Xuguang Zhu1, Sheue-Yann Cheng1
1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Abstract:
Accumulated research has revealed the multifaceted roles of thyroid hormone receptors (TRs) as potent tumor suppressors across various cancer types. This review explores the intricate mechanisms underlying TR-mediated tumor suppression, drawing insights from preclinical mouse models and cancer biology. This review examines the tumor-suppressive functions of TRs, particularly TRβ, in various cancers using preclinical models, revealing their ability to inhibit tumor initiation, progression, and metastasis. Molecular mechanisms underlying TR-mediated tumor suppression are discussed, including interactions with oncogenic signaling pathways like PI3K-AKT, JAK-STAT, and transforming growth factor β. Additionally, this paper examines TRs' effect on cancer stem cell activity and differentiation, showcasing their modulation of key cellular processes associated with tumor progression and therapeutic resistance. Insights from preclinical studies underscore the therapeutic potential of targeting TRs to impede cancer stemness and promote cancer cell differentiation, paving the way for precision medicine in cancer treatment and emphasizing the potential of TR-targeted therapies as promising approaches for treating cancers and improving patient outcomes.
Insights
Thyroid hormone receptors (TRs) act as tumor suppressors, inhibiting cancer growth and spread. Targeting TRs offers a promising strategy for cancer therapy by reducing cancer stemness and promoting differentiation.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Thyroid hormone receptors (TRs) are increasingly recognized for their tumor-suppressive roles in diverse cancers.
- Understanding the molecular mechanisms of TRs is crucial for developing novel cancer therapies.
Purpose of the Study:
- To review the tumor-suppressive functions of TRs, particularly TRβ, across various cancer types.
- To elucidate the molecular mechanisms by which TRs inhibit tumor initiation, progression, and metastasis.
- To explore the impact of TRs on cancer stem cell activity and differentiation.
Main Methods:
- Analysis of preclinical mouse models of cancer.
- Review of molecular biology studies on TRs and oncogenic signaling pathways.
- Examination of TRs' role in cancer stem cell biology and differentiation.
Main Results:
- TRs, especially TRβ, demonstrate potent tumor-suppressive capabilities, inhibiting tumor initiation, progression, and metastasis.
- TRs interact with key oncogenic pathways, including PI3K-AKT, JAK-STAT, and TGF-β.
- TRs modulate cancer stem cell activity and differentiation, influencing therapeutic resistance.
Conclusions:
- TRs play a significant role in suppressing tumor development and progression.
- Targeting TRs presents a viable therapeutic strategy to combat cancer stemness and enhance cancer cell differentiation.
- TR-targeted therapies hold promise for precision medicine and improved patient outcomes in cancer treatment.
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