The stem cell factor (SCF)/c-KIT signalling in testis and prostate cancer

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The stem cell factor (SCF)/c-KIT signalling in testis and prostate cancer

Friday, 22.09.2017

The stem cell factor (SCF)/c-KIT system is involved in the activation of several signal transduction pathways, which culminates in the control of cell proliferation, apoptosis, differentiation and migration in several tissues. The overactivation of c-KIT triggered by several mechanisms has been related to cancer development and progression, mainly leukaemias and gastrointestinal tumours. Recently, in a review published in The Journal of Cell Communication and Signaling, a research team of the Health Sciences Research Centre, University of Beira Interior (CICS-UBI), coordinated by Professor Sílvia Socorro, presented an overview of the signaling pathways activated by SCF/c-KIT in testicular and prostate cancers. Its impact in carcinogenesis and the potential application of c-KIT inhibitors for treatment of these cancer types were discussed.

 

Authors and Affiliations:

Henrique J. Cardoso, Marília I. Figueira, Sílvia Socorro

CICS-UBI, Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal

 

Abstract:

The stem cell factor (SCF) is a cytokine that specifically binds the tyrosine kinase receptor c-KIT. The SCF/c- KIT interaction leads to receptor dimerization, activation of kinase activity and initiation of several signal transduction pathways that control cell proliferation, apoptosis, differentiation and migration in several tissues. The activity of SCF/c-KIT system is linked with the phosphatidylinositol 3-kinase (PI3- K), the Src, the Janus kinase/signal transducers and activators of transcription (JAK/STAT), the phospholipase-C (PLC-γ) and the mitogen-activated protein kinase (MAPK) pathways. Moreover, it has been reported that cancer cases display an overactivation of c-KIT due to the presence of gain-of function mutations or receptor overexpression, which renders c-KIT a tempting target for cancer treatment. In the case of male cancers the most documented activated pathways are the PI3-K and Src, both enhancing abnormal cell proliferation. It is also known that the Src activity in prostate cancer cases depends on the presence of tr-KIT, the cytoplasmic truncated variant of c- KIT that is specifically expressed in tumour tissues and, thus, a very interesting target for drug development. The present review provides an overview of the signalling pathways activated by SCF/c-KIT and discusses the potential application of c-KIT inhibitors for treatment of testicular and prostatic cancers.

 

Journal: Journal of Cell Communication and Signaling

 

Link: https://link.springer.com/article/10.1007%2Fs12079-017-0399-1