Cardoso Henrique J, Figueira Marília I, Correia Sara, Vaz Cátia V, Socorro Sílvia
CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
Mol Reprod Dev. 2014 Dec;81(12):1064-79. doi: 10.1002/mrd.22430. Epub 2014 Oct 30.
Maintaining the delicate balance between cell survival and death is of the utmost importance for the proper development of germ cells and subsequent fertility. On the other hand, the fine regulation of tissue homeostasis by mechanisms that control cell fate is a factor that can prevent carcinogenesis. c-KIT is a type III receptor tyrosine kinase activated by its ligand, stem cell factor (SCF). c-KIT signaling plays a crucial role in cell fate decisions, specifically controlling cell proliferation, differentiation, survival, and apoptosis. Indeed, deregulating the SCF/c-KIT system by attenuation or overactivation of its signaling strength is linked to male infertility and cancer, and rebalancing its activity via c-KIT inhibitors has proven beneficial in treating human tumors that contain gain-of-function mutations or overexpress c-KIT. This review addresses the roles of SCF and c-KIT in the male reproductive tract, and discusses the potential application of c-KIT target therapies in disorders of the reproductive system.
维持细胞存活与死亡之间的微妙平衡对于生殖细胞的正常发育及后续生育能力至关重要。另一方面，通过控制细胞命运的机制对组织稳态进行精细调节是预防癌症发生的一个因素。c-KIT是一种III型受体酪氨酸激酶，由其配体干细胞因子（SCF）激活。c-KIT信号传导在细胞命运决定中起着关键作用，特别是控制细胞增殖、分化、存活和凋亡。事实上，通过减弱或过度激活其信号强度来失调SCF/c-KIT系统与男性不育和癌症有关，并且通过c-KIT抑制剂重新平衡其活性已被证明对治疗含有功能获得性突变或过度表达c-KIT的人类肿瘤有益。本综述阐述了SCF和c-KIT在男性生殖道中的作用，并讨论了c-KIT靶向治疗在生殖系统疾病中的潜在应用。
