Department of Medicine, Albany Medical College, Albany, NY 12208, USA.
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
Genes (Basel). 2020 Jul 7;11(7):755. doi: 10.3390/genes11070755.
The clinical behavior of thyroid cancers is seen to reflect inherent transcriptional activities of mutated genes and trophic effects on tumors of circulating pituitary thyrotropin (TSH). The thyroid hormone, L-thyroxine (T4), has been shown to stimulate proliferation of a large number of different forms of cancer. This activity of T4 is mediated by a cell surface receptor on the extracellular domain of integrin αvβ3. In this brief review, we describe what is known about T4 as a circulating trophic factor for differentiated (papillary and follicular) thyroid cancers. Given T4's cancer-stimulating activity in differentiated thyroid cancers, it was not surprising to find that genomic actions of T4 were anti-apoptotic. Transduction of the T4-generated signal at the integrin primarily involved mitogen-activated protein kinase (MAPK). In thyroid C cell-origin medullary carcinoma of the thyroid (MTC), effects of thyroid hormone analogues, such as tetraiodothyroacetic acid (tetrac), include pro-angiogenic and apoptosis-linked genes. Tetrac is an inhibitor of the actions of T4 at αvβ3, and it is assumed, but not yet proved, that the anti-angiogenic and pro-apoptotic actions of tetrac in MTC cells are matched by T4 effects that are pro-angiogenic and anti-apoptotic. We also note that papillary thyroid carcinoma cells may express the leptin receptor, and circulating leptin from adipocytes may stimulate tumor cell proliferation. Transcription was stimulated by leptin in anaplastic, papillary, and follicular carcinomas of genes involved in invasion, such as matrix metalloproteinases (MMPs). In summary, thyroid hormone analogues may act at their receptor on integrin αvβ3 in a variety of types of thyroid cancer to modulate transcription of genes relevant to tumor invasiveness, apoptosis, and angiogenesis. These effects are independent of TSH.
甲状腺癌的临床行为被认为反映了突变基因的固有转录活性和循环垂体促甲状腺素 (TSH) 对肿瘤的营养作用。甲状腺激素 L-甲状腺素 (T4) 已被证明可刺激大量不同形式的癌症增殖。这种 T4 的活性是通过整合素 αvβ3 细胞外结构域上的细胞表面受体介导的。在这篇简短的综述中，我们描述了 T4 作为分化型（乳头状和滤泡状）甲状腺癌的循环营养因子的作用。鉴于 T4 在分化型甲状腺癌中的促癌活性，发现 T4 的基因组作用具有抗细胞凋亡作用并不奇怪。T4 产生的信号在整合素上的转导主要涉及丝裂原活化蛋白激酶 (MAPK)。在甲状腺 C 细胞起源的甲状腺髓样癌 (MTC) 中，甲状腺激素类似物（如四碘甲状腺乙酸 (tetrac)）的作用包括促血管生成和与凋亡相关的基因。Tetrac 是 T4 在 αvβ3 上作用的抑制剂，并且假设（但尚未证明）tetrac 在 MTC 细胞中的抗血管生成和促凋亡作用与 T4 的促血管生成和抗细胞凋亡作用相匹配。我们还注意到，乳头状甲状腺癌细胞可能表达瘦素受体，来自脂肪细胞的循环瘦素可能刺激肿瘤细胞增殖。转录在涉及侵袭的基因中，如基质金属蛋白酶 (MMPs)，被瘦素刺激在间变性、乳头状和滤泡状癌中。总之，甲状腺激素类似物可能通过其在整合素 αvβ3 上的受体作用于各种类型的甲状腺癌，调节与肿瘤侵袭性、细胞凋亡和血管生成相关的基因转录。这些作用与 TSH 无关。
