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Journal of Cell Communication and Signaling

, Volume 11, Issue 4, pp 297–307 | Cite as

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

  • Henrique J. Cardoso
  • Marília I. Figueira
  • Sílvia Socorro
Research Article

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.

Keywords

C-KIT KIT ligand Prostate cancer SCF Signalling Testicular cancer 

Abbreviations

ERK

Extracellular-signal-regulated kinase

GNNK

Gly-Asn-Asn-Lys

Grb2

Growth factor receptor bound protein-2

JAK

Janus kinase

JNK

c-Jun N-terminal kinase

MAPK

Mitogen-activated protein kinase

mSCF

membrane-bound SCF

mTOR

mammalian target of rapamycin

p70S6K

p70 S6 kinase

PI3-K

Phosphatidylinositol 3-kinase

PLC-γ

phospholipase-C

Rb

Retinoblastoma

SCF

Stem cell factor

SH2

Src homology 2

sSCF

soluble SCF

STAT

Signal transducers and activators of transcription

tr-KIT

truncated c-KIT protein

Notes

Acknowledgments

This work was supported by FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation (Project No. 007491) and National Funds by FCT-Foundation for Science and Technology (Project UID/Multi/00709/2013). Henrique Cardoso and Marília Figueira were funded by FCT fellowships (SFRH/BD/ 111351/2015 and SFRH/BD/104671/2014, respectively).

The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

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© The International CCN Society 2017

Authors and Affiliations

  1. 1.CICS-UBI, Centro de Investigação em Ciências da SaúdeUniversidade da Beira InteriorCovilhãPortugal

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