The SCF/c-KIT system in the male: Survival strategies in fertility and cancer

Abstract

SUMMARY 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. Mol. Reprod. Dev. 81: 1064–1079, 2014. © 2014 Wiley Periodicals, Inc.

c-Kit as a Novel Potential Therapeutic Target in Colorectal Cancer

“…3 These studies revealed the tremendous proliferative ability of the hepatocyte, with an almost unlimited clonogenic potential. 4,5 In contrast, BA levels need to be finely tuned to avoid their excess and hepatic toxicity. 3 Such findings indicate the existence of mechanisms that tightly control the onset and termination of adult liver growth, namely, a "hepatostat," or specific sensors that maintain the proper liver size.…”

Aging-associated changes in oxidative stress, cell proliferation, and apoptosis are prevented in the prostate of transgenic rats overexpressing regucalcin

“…It is known that the tyrosine kinase receptor c-kit on the binding of SCF activates several intracellular signaling cascades that promote cell proliferation. 22 Interestingly, the mRNA expression of SCF and c-kit is diminished in 9-M Tg-RGN relatively to the corresponding wild-type group. In addition, aging reduced the expression of SCF and c-kit in Tg-RGN, whereas c-kit levels remained unchanged in wild-type animals (Fig 3, A and Fig 3, B).…”

“…The stem cell factor (SCF) and its Translational Research tyrosine kinase receptor c-kit are powerful regulators of cell proliferation, which also have been associated with the control of prostate cell growth. 22 The mRNA expression of SCF is significantly lower in aged wildtype animals (0.65 6 0.10 fold; Fig 3, A). In addition, 3-and 9-M Tg-RGN groups displayed reduced expression of SCF mRNA relatively to their agematched counterparts (0.62 6 0.07 and 0.36 6 0.05 fold, respectively; Fig 3, A), which means an approximately 40% reduction of SCF with increasing age (P , 0.05).…”

MiR‐4485‐3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia

“…The mutation in tyrosine receptor kinase, KIT, mostly reported in cancer; however, several single-nucleotide polymorphisms (SNPs) in this gene reported that were associated with oligospermia and azoospermia (Cheng, Chen, Liu, Pu, & Zhou Cun, 2013;Galan et al, 2006). The KIT protein and its ligand stem cell factor (SCF) involved in growth and survival of germinal cells and alteration in the expression of these genes lead to infertility (Correia, Alves, Cavaco, Oliveira, & Socorro, 2014;Figueira, Cardoso, Correia, Maia, & Socorro, 2014) maybe through imbalance between death and survival (Cardoso, Figueira, Correia, Vaz, & Socorro, 2014). PARK7 gene encodes DJ-1 protein that expressed ubiquitously; nonetheless, its expression specifically high in testis (Nagakubo et al, 1997).…”