» Articles » PMID: 28656507

The Stem Cell Factor (SCF)/c-KIT Signalling in Testis and Prostate Cancer

Overview
Date 2017 Jun 29
PMID 28656507
Citations 25
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Biological and therapeutic implications of sex hormone-related gene clustering in testicular cancer.

Torzsok P, Santer F, Kunz Y, van Creij N, Tymoszuk P, Klinglmair G Basic Clin Androl. 2025; 35(1):8.

PMID: 40011822 PMC: 11863433. DOI: 10.1186/s12610-025-00254-5.


Exocyst complex component 1 (Exoc1) loss in dormant oocyte disrupts c-KIT and growth differentiation factor (GDF9) subcellular localization and causes female infertility in mice.

Nguyen C, Kuba Y, Le H, Shawki H, Mikami N, Aoki M Cell Death Discov. 2025; 11(1):17.

PMID: 39833146 PMC: 11747099. DOI: 10.1038/s41420-025-02291-5.


Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1.

Kalkan K, Yalcin B, Cengiz Mat O, Yay A Medeni Med J. 2024; 39(4):283-292.

PMID: 39726526 PMC: 11683295. DOI: 10.4274/MMJ.galenos.2024.04932.


NR4A1 and NR4A2 orphan nuclear receptors regulate endothelial-to-hematopoietic transition in mouse hematopoietic stem cell specification.

Sa da Bandeira D, Nevitt C, Segato Dezem F, Marcao M, Liu Y, Kelley Z Development. 2024; 151(22).

PMID: 39589268 PMC: 11634030. DOI: 10.1242/dev.201957.


Stem cell factor restrains endoplasmic reticulum stress-associated apoptosis through c-Kit receptor activation of JAK2/STAT3 axis in hippocampal neuronal cells.

Shen H, Nie J, Li G, Tian H, Zhang J, Luo X PLoS One. 2024; 19(11):e0310872.

PMID: 39546459 PMC: 11567559. DOI: 10.1371/journal.pone.0310872.


References
1.
Tian Q, Frierson Jr H, Krystal G, Moskaluk C . Activating c-kit gene mutations in human germ cell tumors. Am J Pathol. 1999; 154(6):1643-7. PMC: 1876773. DOI: 10.1016/S0002-9440(10)65419-3. View

2.
Thommes K, Lennartsson J, Carlberg M, Ronnstrand L . Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor. Biochem J. 1999; 341 ( Pt 1):211-6. PMC: 1220349. View

3.
Mou S, Linnekin D . Lyn is activated during late G1 of stem-cell-factor-induced cell cycle progression in haemopoietic cells. Biochem J. 1999; 342 ( Pt 1):163-70. PMC: 1220449. View

4.
Caruana G, Cambareri A, Ashman L . Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts. Oncogene. 1999; 18(40):5573-81. DOI: 10.1038/sj.onc.1202939. View

5.
Feng L, Ravindranath N, Dym M . Stem cell factor/c-kit up-regulates cyclin D3 and promotes cell cycle progression via the phosphoinositide 3-kinase/p70 S6 kinase pathway in spermatogonia. J Biol Chem. 2000; 275(33):25572-6. DOI: 10.1074/jbc.M002218200. View