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

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.

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Fig. 1
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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

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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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Correspondence to Sílvia Socorro.

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Cardoso, H.J., Figueira, M.I. & Socorro, S. The stem cell factor (SCF)/c-KIT signalling in testis and prostate cancer. J. Cell Commun. Signal. 11, 297–307 (2017). https://doi.org/10.1007/s12079-017-0399-1

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Keywords

  • C-KIT
  • KIT ligand
  • Prostate cancer
  • SCF
  • Signalling
  • Testicular cancer