胰岛素受体亚型和胰岛素生长因子样受体：对细胞信号传导、癌发生和化疗耐药的影响,International Journal of Molecular Sciences

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胰岛素受体亚型和胰岛素生长因子样受体：对细胞信号传导、癌发生和化疗耐药的影响
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2023-10-09 , DOI: 10.3390/ijms241915006
Mariam Ahmed Galal _{1,

2} , Samhar Samer Alouch ₁ , Buthainah Saad Alsultan ₁ , Huda Dahman ₁ , Nouf Abdullah Alyabis ₁ , Sarah Ammar Alammar ₁ , Ahmad Aljada ₁

Affiliation

这篇全面的综述全面探讨了胰岛素受体 (IR) 亚型和胰岛素样生长因子受体 (IGFR) 在胰岛素和胰岛素样生长因子 (IGF) 信号传导 (IIS) 途径中的复杂参与。这个复杂的系统包含配体、受体和结合蛋白，产生广泛的功能，包括致癌和化疗耐药等方面。IR 和 IGFR 结构的详细遗传分析突出了它们不同的同种型，这些同种型由选择性剪接产生，并表现出对配体的不同亲和力。值得注意的是，IR-A 亚型的过度表达与癌症干性、肿瘤发展和对靶向治疗的耐药性有关。同样，IGFR 表达升高会加速肿瘤进展并促进化疗耐药。该综述强调了 IR 和 IGFR 之间复杂的相互作用，导致抗 IGFR 药物产生耐药性。因此，两种受体的双重靶向可能为克服化疗耐药性提供更有效的策略。总之，这篇综述揭示了 IR 和 IGFR 在细胞信号传导、致癌和治疗耐药中发挥的关键作用。通过精确调节这些受体及其复杂的信号通路，有可能开发出增强的抗癌干预措施，最终改善患者的治疗效果。

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Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance

This comprehensive review thoroughly explores the intricate involvement of insulin receptor (IR) isoforms and insulin-like growth factor receptors (IGFRs) in the context of the insulin and insulin-like growth factor (IGF) signaling (IIS) pathway. This elaborate system encompasses ligands, receptors, and binding proteins, giving rise to a wide array of functions, including aspects such as carcinogenesis and chemoresistance. Detailed genetic analysis of IR and IGFR structures highlights their distinct isoforms, which arise from alternative splicing and exhibit diverse affinities for ligands. Notably, the overexpression of the IR-A isoform is linked to cancer stemness, tumor development, and resistance to targeted therapies. Similarly, elevated IGFR expression accelerates tumor progression and fosters chemoresistance. The review underscores the intricate interplay between IRs and IGFRs, contributing to resistance against anti-IGFR drugs. Consequently, the dual targeting of both receptors could present a more effective strategy for surmounting chemoresistance. To conclude, this review brings to light the pivotal roles played by IRs and IGFRs in cellular signaling, carcinogenesis, and therapy resistance. By precisely modulating these receptors and their complex signaling pathways, the potential emerges for developing enhanced anti-cancer interventions, ultimately leading to improved patient outcomes.

更新日期：2023-10-09

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