Zaeifi Davood, Jamialahmadi Khadijeh, Karimi Gholamreza
Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Biotechnology Research Center, Pharmaceutical Technology Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Mol Med. 2025 Jul;29(14):e70737. doi: 10.1111/jcmm.70737.
p66Shc is a redox-sensitive and pro-apoptotic adaptor protein that regulates oxidative stress and mitochondrial apoptosis. It is the largest of three isoforms encoded by the proto-oncogene ShcA (Src collagen homologue A). Members of the ShcA family are capable of recruiting various signalling molecules and are involved in several cellular pathways, including proliferation, growth and survival. Increasing evidence highlights the p66Shc role in various tumourigenic processes, such as cell expansion, progression, metastasis and metabolic reprogramming. This review summarises current knowledge on the role of p66Shc in cancer, explains the molecular mechanisms underlying the effects of this protein, and considers therapeutic prospects aimed at targeting it. Emerging therapeutic strategies, including small-molecule inhibitors and gene-editing approaches, are discussed alongside challenges in clinical translation.
p66Shc是一种对氧化还原敏感的促凋亡衔接蛋白，可调节氧化应激和线粒体凋亡。它是原癌基因ShcA（Src胶原同源物A）编码的三种异构体中最大的一种。ShcA家族成员能够募集各种信号分子，并参与多种细胞途径，包括增殖、生长和存活。越来越多的证据凸显了p66Shc在各种肿瘤发生过程中的作用，如细胞扩张、进展、转移和代谢重编程。本综述总结了目前关于p66Shc在癌症中作用的知识，解释了该蛋白作用的分子机制，并探讨了针对它的治疗前景。同时讨论了包括小分子抑制剂和基因编辑方法在内的新兴治疗策略以及临床转化中的挑战。
