Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Endocrinology. 2024 Aug 27;165(10). doi: 10.1210/endocr/bqae115.
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.
积累的研究揭示了甲状腺激素受体 (TRs) 在多种癌症类型中作为强大肿瘤抑制因子的多方面作用。本综述探讨了 TR 介导的肿瘤抑制的复杂机制,从临床前小鼠模型和癌症生物学中汲取了见解。本综述使用临床前模型研究了 TRs(特别是 TRβ)在各种癌症中的肿瘤抑制功能,揭示了它们抑制肿瘤起始、进展和转移的能力。讨论了 TR 介导的肿瘤抑制的分子机制,包括与 PI3K-AKT、JAK-STAT 和转化生长因子 β 等致癌信号通路的相互作用。此外,本文还研究了 TRs 对癌症干细胞活性和分化的影响,展示了它们对与肿瘤进展和治疗耐药性相关的关键细胞过程的调节。临床前研究的见解强调了靶向 TR 以抑制癌症干性和促进癌症细胞分化的治疗潜力,为癌症治疗中的精准医学铺平了道路,并强调了 TR 靶向治疗作为治疗癌症和改善患者预后的有前途方法的潜力。