Commonalities of survival strategies employed by germ and cancer cells: the case of SCF/c-KIT system

The tyrosine kinase receptor, c-KIT, and its ligand, the stem cell factor (SCF), constitute a powerful system in the control of cell survival and proliferation. In a recent review published in Molecular Reproduction and Development the MSc students Henrique Cardoso and Marília Figueira, under supervision of Professor Sílvia Socorro, discussed the function of SCF and c-KIT in spermatogenesis and cancer, highlighting the similarities between germ and cancer cells. The SCF/c-KIT system is present throughout the distinct development stages of spermatogenesis, and its deregulated expression has been associated with male infertility. Also, c-KIT overexpression and/or gain-of-function mutations are strongly associated with the onset of testicular and prostatic cancers. Thereby, the application of c-KIT targeting therapies in male reproductive disorders has gained importance over the last years.

Authors and Affiliations:

Henrique J. Cardoso, Marília I. Figueira, Sara Correia, Cátia V. Vaz and Sílvia Socorro

CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal

Abstract:

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

Journal: Molecular Reproduction and Development

Link: http://onlinelibrary.wiley.com/doi/10.1002/mrd.22430/abstract