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Role of thyroid hormone-integrin αvβ3-signal and therapeutic strategies in colorectal cancers
Journal of Biomedical Science ( IF 9.0 ) Pub Date : 2021-04-08 , DOI: 10.1186/s12929-021-00719-5
Yu-Chen S. H. Yang , Po-Jui Ko , Yi-Shin Pan , Hung-Yun Lin , Jacqueline Whang-Peng , Paul J. Davis , Kuan Wang

Thyroid hormone analogues—particularly, l-thyroxine (T4) has been shown to be relevant to the functions of a variety of cancers. Integrin αvβ3 is a plasma membrane structural protein linked to signal transduction pathways that are critical to cancer cell proliferation and metastasis. Thyroid hormones, T4 and to a less extend T3 bind cell surface integrin αvβ3, to stimulate the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway to stimulate cancer cell growth. Thyroid hormone analogues also engage in crosstalk with the epidermal growth factor receptor (EGFR)-Ras pathway. EGFR signal generation and, downstream, transduction of Ras/Raf pathway signals contribute importantly to tumor cell progression. Mutated Ras oncogenes contribute to chemoresistance in colorectal carcinoma (CRC); chemoresistance may depend in part on the activity of ERK1/2 pathway. In this review, we evaluate the contribution of thyroxine interacting with integrin αvβ3 and crosstalking with EGFR/Ras signaling pathway non-genomically in CRC proliferation. Tetraiodothyroacetic acid (tetrac), the deaminated analogue of T4, and its nano-derivative, NDAT, have anticancer functions, with effectiveness against CRC and other tumors. In Ras-mutant CRC cells, tetrac derivatives may overcome chemoresistance to other drugs via actions initiated at integrin αvβ3 and involving, downstream, the EGFR-Ras signaling pathways.

中文翻译:

甲状腺激素-整合素αvβ3-信号和治疗策略在结直肠癌中的作用

甲状腺激素类似物——尤其是 l-甲状腺素 (T4) 已被证明与多种癌症的功能有关。整合素 αvβ3 是一种质膜结构蛋白,与对癌细胞增殖和转移至关重要的信号转导通路相关。甲状腺激素、T4 和较少范围的 T3 结合细胞表面整合素 αvβ3,以刺激细胞外信号调节激酶 1/2 (ERK1/2) 途径以刺激癌细胞生长。甲状腺激素类似物也参与与表皮生长因子受体 (EGFR)-Ras 通路的串扰。EGFR 信号的产生和下游 Ras/Raf 通路信号的转导对肿瘤细胞的进展有重要贡献。突变的 Ras 癌基因导致结直肠癌 (CRC) 的化学抗性;化学抗性可能部分取决于 ERK1/2 通路的活性。在这篇综述中,我们评估了甲状腺素与整合素 αvβ3 相互作用以及与 EGFR/Ras 信号通路的非基因组串扰在 CRC 增殖中的贡献。T4 的脱氨基类似物四碘甲腺乙酸 (tetraiodothyroacetate, tetrac) 及其纳米衍生物 NDAT 具有抗癌功能,对结直肠癌和其他肿瘤有效。在 Ras 突变的 CRC 细胞中,tetrac 衍生物可以通过在整联蛋白 αvβ3 处启动并涉及下游 EGFR-Ras 信号通路的作用来克服对其他药物的化学抗性。其纳米衍生物NDAT具有抗癌功能,对结直肠癌等肿瘤有效。在 Ras 突变的 CRC 细胞中,tetrac 衍生物可以通过在整联蛋白 αvβ3 处启动并涉及下游 EGFR-Ras 信号通路的作用来克服对其他药物的化学抗性。其纳米衍生物NDAT具有抗癌功能,对结直肠癌等肿瘤有效。在 Ras 突变的 CRC 细胞中,tetrac 衍生物可以通过在整联蛋白 αvβ3 处启动并涉及下游 EGFR-Ras 信号通路的作用来克服对其他药物的化学抗性。
更新日期:2021-04-08
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