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.
Similar content being viewed by others
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
References
Aksamitiene E, Kiyatkin A, Kholodenko BN (2012) Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance. Biochem Soc Trans 40:139–146
Ali S, Ali S (2007) Role of c-kit/SCF in cause and treatment of gastrointestinal stromal tumors (GIST). Gene 401:38–45
Ashman LK, Griffith R (2013) Therapeutic targeting of c-KIT in cancer. Expert Opin Investig Drugs 22:103–115
Biermann K, Goke F, Nettersheim D, Eckert D, Zhou H, Kahl P, Gashaw I, Schorle H, Buttner R (2007) C-KIT is frequently mutated in bilateral germ cell tumours and down-regulated during progression from intratubular germ cell neoplasia to seminoma. J Pathol 213:311–318
Birnie R, Bryce SD, Roome C, Dussupt V, Droop A, Lang SH, Berry PA, Hyde CF, Lewis JL, Stower MJ, Maitland NJ, Collins AT (2008) Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions. Genome Biol 9:R83
Blume-Jensen P, Hunter T (2001) Oncogenic kinase signalling. Nature 411:355–365
Blume-Jensen P, Janknecht R, Hunter T (1998) The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of bad on Ser136. Curr Biol 8:779–782
Capelli L, Petracci E, Quagliuolo V, Saragoni L, Colombo P, Morgagni P, Calistri D, Tomezzoli A, Di Cosmo M, Roviello F, Vindigni C, Coniglio A, Villanacci V, Catarci M, Coppola L, Alfieri S, Ricci R, Capella C, Rausei S, Gulino D, Amadori D, Ulivi P (2016) Gastric GISTs: analysis of c-kit, PDGFRA and BRAF mutations in relation to prognosis and clinical pathological characteristics of patients - a GIRCG study. European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 42:1206–1214
Cardoso HJ, Figueira MI, Correia S, Vaz CV, Socorro S (2014) The SCF/c-KIT system in the male: survival strategies in fertility and cancer. Mol Reprod Dev 81:1064–1079
Cardoso HJ, Vaz CV, Correia S, Figueira MI, Marques R, Maia CJ, Socorro S (2015) Paradoxical and contradictory effects of imatinib in two cell line models of hormone-refractory prostate cancer. Prostate 75:923–935
Caruana G, Cambareri AC, Ashman LK (1999) Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts. Oncogene 18:5573–5581
Ceder JA, Aalders TW, Schalken JA (2017) Label retention and stem cell marker expression in the developing and adult prostate identifies basal and luminal epithelial stem cell subpopulations. Stem Cell Res Ther 8:95
Chieffi P (2014) Recent advances in molecular and cell biology of testicular germ-cell tumors. Int Rev Cell Mol Biol 312:79–100
Coffey J, Linger R, Pugh J, Dudakia D, Sokal M, Easton DF, Timothy Bishop D, Stratton M, Huddart R, Rapley EA (2008) Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature. Genes, chromosomes & cancer 47:34–42
Corcoran NM, Costello AJ (2005) Combined low-dose imatinib mesylate and paclitaxel lack synergy in an experimental model of extra-osseous hormone-refractory prostate cancer. BJU Int 96:640–646
Dahlen DD, Lin NL, Liu YC, Broudy VC (2001) Soluble kit receptor blocks stem cell factor bioactivity in vitro. Leuk Res 25:413–421
Damaschke NA, Yang B, Bhusari S, Svaren JP, Jarrard DF (2013) Epigenetic susceptibility factors for prostate cancer with aging. Prostate 73:1721–1730
De Miguel MP, Cheng L, Holland EC, Federspiel MJ, Donovan PJ (2002) Dissection of the c-kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer. Proc Natl Acad Sci U S A 99:10458–10463
Deberry C, Mou S, Linnekin D (1997) Stat1 associates with c-kit and is activated in response to stem cell factor. Biochem J 327:73–80
Derry JJ, Prins GS, Ray V, Tyner AL (2003) Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. Oncogene 22:4212–4220
Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26:3279–3290
Di Lorenzo G, Autorino R, D'Armiento FP, Mignogna C, De Laurentiis M, De Sio M, D'Armiento M, Damiano R, Vecchio G, De Placido S (2004) Expression of proto-oncogene c-kit in high risk prostate cancer. European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 30:987–992
Dolci S, Pellegrini M, Di Agostino S, Geremia R, Rossi P (2001) Signaling through extracellular signal-regulated kinase is required for spermatogonial proliferative response to stem cell factor. J Biol Chem 276:40225–40233
Farini D, La Sala G, Tedesco M, De Felici M (2007) Chemoattractant action and molecular signaling pathways of kit ligand on mouse primordial germ cells. Dev Biol 306:572–583
Farooqi AA, Sarkar FH (2015) Overview on the complexity of androgen receptor-targeted therapy for prostate cancer. Cancer Cell Int 15:7
Fayyaz S, Farooqi AA (2013) miRNA and TMPRSS2-ERG do not mind their own business in prostate cancer cells. Immunogenetics 65:315–332
Feng LX, Ravindranath N, Dym M (2000) 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 275:25572–25576
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403
Figueira MI, Cardoso HJ, Correia S, Maia CJ, Socorro S (2014) Hormonal regulation of c-KIT receptor and its ligand: implications for human infertility? Prog Histochem Cytochem 49:1–19
Filippou P, Ferguson JE 3rd, Nielsen ME (2016) Epidemiology of prostate and testicular cancer. Semin Interv Radiol 33:182–185
Fukao T, Yamada T, Tanabe M, Terauchi Y, Ota T, Takayama T, Asano T, Takeuchi T, Kadowaki T, Hata Ji J, Koyasu S (2002) Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice. Nat Immunol 3:295–304
Gommerman JL, Sittaro D, Klebasz NZ, Williams DA, Berger SA (2000) Differential stimulation of c-kit mutants by membrane-bound and soluble steel factor correlates with leukemic potential. Blood 96:3734–3742
Hayes-Lattin B, Nichols CR (2009) Testicular cancer: a prototypic tumor of young adults. Semin Oncol 36:432–438
Huang DY, Chao Y, Tai MH, Yu YH, Lin WW (2012) STI571 reduces TRAIL-induced apoptosis in colon cancer cells: c-Abl activation by the death receptor leads to stress kinase-dependent cell death. J Biomed Sci 19:35
Imura M, Kojima Y, Kubota Y, Hamakawa T, Yasui T, Sasaki S, Hayashi Y, Kohri K (2012) Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia. Prostate 72:1506–1513
Izquierdo MA, Van der Valk P, Van Ark-Otte J, Rubio G, Germa-Lluch JR, Ueda R, Scheper RJ, Takahashi T, Giaccone G (1995) Differential expression of the c-kit proto-oncogene in germ cell tumours. J Pathol 177:253–258
Kapur R, Chandra S, Cooper R, McCarthy J, Williams DA (2002) Role of p38 and ERK MAP kinase in proliferation of erythroid progenitors in response to stimulation by soluble and membrane isoforms of stem cell factor. Blood 100:1287–1293
Kemmer K, Corless CL, Fletcher JA, McGreevey L, Haley A, Griffith D, Cummings OW, Wait C, Town A, Heinrich MC (2004) KIT mutations are common in testicular seminomas. Am J Pathol 164:305–313
Kerr IM, Costa-Pereira AP, Lillemeier BF, Strobl B (2003) Of JAKs, STATs, blind watchmakers, jeeps and trains. FEBS Lett 546:1–5
Klippel A, Escobedo JA, Hirano M, Williams LT (1994) The interaction of small domains between the subunits of phosphatidylinositol 3-kinase determines enzyme activity. Mol Cell Biol 14:2675–2685
Koike T, Hirai K, Morita Y, Nozawa Y (1993) Stem cell factor-induced signal transduction in rat mast cells. Activation of phospholipase D but not phosphoinositide-specific phospholipase C in c-kit receptor stimulation J Immunol 151:359–366
Kuang D, Zhao X, Xiao G, Ni J, Feng Y, Wu R, Wang G (2008) Stem cell factor/c-kit signaling mediated cardiac stem cell migration via activation of p38 MAPK. Basic Res Cardiol 103:265–273
Langley KE, Mendiaz EA, Liu N, Narhi LO, Zeni L, Parseghian CM, Clogston CL, Leslie I, Pope JA, Lu HS, Zsebo KM, Boone TC (1994) Properties of variant forms of human stem cell factor recombinantly expressed in Escherichia coli. Arch Biochem Biophys 311:55–61
Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141:1117–1134
Lemmon MA, Pinchasi D, Zhou M, Lax I, Schlessinger J (1997) Kit receptor dimerization is driven by bivalent binding of stem cell factor. J Biol Chem 272:6311–6317
Lennartsson J, Ronnstrand L (2012) Stem cell factor receptor/c-kit: from basic science to clinical implications. Physiol Rev 92:1619–1649
Leong KG, Wang BE, Johnson L, Gao WQ (2008) Generation of a prostate from a single adult stem cell. Nature 456:804–808
Lin X, Aslam A, Attar R, Yaylim I, Qureshi MZ, Hasnain S, Qadir MI, and Farooqi AA (2016a) Signaling lansdscape of prostate cancer. Cellular and molecular biology (noisy-le-grand, France) 62:45-50
Lin X, Farooqi AA, Qureshi MZ, Romero MA, Tabassum S, Ismail M (2016b) Prostate cancer stem cells: viewing signaling cascades at a finer resolution. Arch Immunol Ther Exp 64:217–223
Linnekin D, DeBerry CS, Mou S (1997a) Lyn associates with the juxtamembrane region of c-kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells. J Biol Chem 272:27450–27455
Linnekin D, Mou S, Deberry CS, Weiler SR, Keller JR, Ruscetti FW, Longo DL (1997b) Stem cell factor, the JAK-STAT pathway and signal transduction. Leuk Lymphoma 27:439–444
Lipton A, Campbell-Baird C, Harvey H, Kim C, Demers L, Costa L (2010) Phase I trial of zoledronic acid + imatinib mesylate (Gleevec) in patients with bone metastases. Am J Clin Oncol 33:75–78
Maddens S, Charruyer A, Plo I, Dubreuil P, Berger S, Salles B, Laurent G, Jaffrezou JP (2002) Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gamma 1: implication in stem cell factor radioprotective effect. Blood 100:1294–1301
Mansuroglu T, Ramadori P, Dudas J, Malik I, Hammerich K, Fuzesi L, Ramadori G (2009) Expression of stem cell factor and its receptor c-kit during the development of intrahepatic cholangiocarcinoma. Lab Investig 89:562–574
Maruyama IN (2014) Mechanisms of activation of receptor tyrosine kinases: monomers or dimers. Cells 3:304–330
Mathew P, Thall PF, Jones D, Perez C, Bucana C, Troncoso P, Kim SJ, Fidler IJ, Logothetis C (2004) Platelet-derived growth factor receptor inhibitor imatinib mesylate and docetaxel: a modular phase I trial in androgen-independent prostate cancer. J Clin Oncol 22:3323–3329
Mitchell SG, Bunting ST, Saxe D, Olson T, and Keller FG (2017) A variant c-KIT mutation, D816H, fundamental to the sequential development of an ovarian mixed germ cell tumor and systemic mastocytosis with chronic myelomonocytic leukemia. Pediatric blood & cancer 64
Miyazawa K, Williams DA, Gotoh A, Nishimaki J, Broxmeyer HE, Toyama K (1995) Membrane-bound steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form. Blood 85:641–649
Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, McRee DE (2003) Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem 278:31461–31464
Montero JC, Lopez-Perez R, San Miguel JF, Pandiella A (2008) Expression of c-kit isoforms in multiple myeloma: differences in signaling and drug sensitivity. Haematologica 93:851–859
Mou S, Linnekin D (1999) Lyn is activated during late G1 of stem-cell-factor-induced cell cycle progression in haemopoietic cells. Biochem J 342(Pt 1):163–170
Nabhan C, Villines D, Valdez TV, Tolzien K, Lestingi TM, Bitran JD, Christner SM, Egorin MJ, Beumer JH (2012) Phase I study investigating the safety and feasibility of combining imatinib mesylate (Gleevec) with sorafenib in patients with refractory castration-resistant prostate cancer. Br J Cancer 107:592–597
Nakai Y, Nonomura N, Oka D, Shiba M, Arai Y, Nakayama M, Inoue H, Nishimura K, Aozasa K, Mizutani Y, Miki T, Okuyama A (2005) KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors. Biochem Biophys Res Commun 337:289–296
Nishida K, Wang L, Morii E, Park SJ, Narimatsu M, Itoh S, Yamasaki S, Fujishima M, Ishihara K, Hibi M, Kitamura Y, Hirano T (2002) Requirement of Gab2 for mast cell development and KitL/c-kit signaling. Blood 99:1866–1869
O'Laughlin-Bunner B, Radosevic N, Taylor ML, Shivakrupa DBC, Metcalfe DD, Zhou M, Lowell C, Linnekin D (2001) Lyn is required for normal stem cell factor-induced proliferation and chemotaxis of primary hematopoietic cells. Blood 98:343–350
Paronetto MP, Venables JP, Elliott DJ, Geremia R, Rossi P, Sette C (2003) Tr-kit promotes the formation of a multimolecular complex composed by Fyn, PLCgamma1 and Sam68. Oncogene 22:8707–8715
Paronetto MP, Farini D, Sammarco I, Maturo G, Vespasiani G, Geremia R, Rossi P, Sette C (2004) Expression of a truncated form of the c-kit tyrosine kinase receptor and activation of Src kinase in human prostatic cancer. Am J Pathol 164:1243–1251
Paulhe F, Wehrle-Haller M, Jacquier MC, Imhof BA, Tabone-Eglinger S, Wehrle-Haller B (2009) Dimerization of kit-ligand and efficient cell-surface presentation requires a conserved Ser-Gly-Gly-Tyr motif in its transmembrane domain. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 23:3037–3048
Pedersini R, Vattemi E, Mazzoleni G, Graiff C (2007) Complete response after treatment with imatinib in pretreated disseminated testicular seminoma with overexpression of c-KIT. Lancet Oncol 8:1039–1040
Peng Y, Chen Q, Gu M, Chen Y, Zhang M, Zhou J, Wang H, Gao Y, Li W, Wang Z, Cai Z (2015) Human stromal cells in the peripheral zone of the prostate promote tumorigenesis of prostatic cancer stem cells through up-regulation of C-kit expression. J Cancer 6:776–785
Phung B, Steingrimsson E, Ronnstrand L (2013) Differential activity of c-KIT splice forms is controlled by extracellular peptide insert length. Cell Signal 25:2231–2238
Piao X, Bernstein A (1996) A point mutation in the catalytic domain of c-kit induces growth factor independence, tumorigenicity, and differentiation of mast cells. Blood 87:3117–3123
Pinto AC, Angelo S, Moreira JN, Simoes S (2011) Schedule treatment design and quantitative in vitro evaluation of chemotherapeutic combinations for metastatic prostate cancer therapy. Cancer Chemother Pharmacol 67:275–284
Price DJ, Rivnay B, Fu Y, Jiang S, Avraham S, Avraham H (1997) Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes. J Biol Chem 272:5915–5920
Rapley EA, Hockley S, Warren W, Johnson L, Huddart R, Crockford G, Forman D, Leahy MG, Oliver DT, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Heidenreich A, Geczi L, Bodrogi I, Olah E, Ormiston WJ, Daly PA, Looijenga LH, Guilford P, Aass N, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Einhorn L, Weber BL, McMaster M, Greene MH, Bishop DT, Easton D, Stratton MR (2004) Somatic mutations of KIT in familial testicular germ cell tumours. Br J Cancer 90:2397–2401
Robinson DR, Wu YM, Lin SF (2000) The protein tyrosine kinase family of the human genome Oncogene 19:5548–5557
Ronnstrand L (2004) Signal transduction via the stem cell factor receptor/c-kit. Cell Mol Life Sci 61:2535–2548
Rossi P, Marziali G, Albanesi C, Charlesworth A, Geremia R, Sorrentino V (1992) A novel c-kit transcript, potentially encoding a truncated receptor, originates within a kit gene intron in mouse spermatids. Dev Biol 152:203–207
Ryan JJ, Huang H, McReynolds LJ, Shelburne C, Hu-Li J, Huff TF, Paul WE (1997) Stem cell factor activates STAT-5 DNA binding in IL-3-derived bone marrow mast cells. Exp Hematol 25:357–362
Sakuma Y, Sakurai S, Oguni S, Hironaka M, Saito K (2003) Alterations of the c-kit gene in testicular germ cell tumors. Cancer Sci 94:486–491
Samayawardhena LA, Kapur R, Craig AW (2007) Involvement of Fyn kinase in kit and integrin-mediated Rac activation, cytoskeletal reorganization, and chemotaxis of mast cells. Blood 109:3679–3686
Schnabel D, Ramirez L, Gertsenstein M, Nagy A, Lomeli H (2005) Ectopic expression of KitD814Y in spermatids of transgenic mice, interferes with sperm morphogenesis. Developmental dynamics: an official publication of the American Association of Anatomists 233:29–40
Segaliny AI, Tellez-Gabriel M, Heymann MF, Heymann D (2015) Receptor tyrosine kinases: Characterisation, mechanism of action and therapeutic interests for bone cancers. Journal of Bone Oncology 4:1–12
Serve H, Hsu YC, Besmer P (1994) Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells. J Biol Chem 269:6026–6030
Serve H, Yee NS, Stella G, Sepp-Lorenzino L, Tan JC, Besmer P (1995) Differential roles of PI3-kinase and kit tyrosine 821 in kit receptor-mediated proliferation, survival and cell adhesion in mast cells. EMBO J 14:473–483
Sette C, Bevilacqua A, Geremia R, Rossi P (1998) Involvement of phospholipase Cgamma1 in mouse egg activation induced by a truncated form of the C-kit tyrosine kinase present in spermatozoa. J Cell Biol 142:1063–1074
Sette C, Paronetto MP, Barchi M, Bevilacqua A, Geremia R, Rossi P (2002) Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase. EMBO J 21:5386–5395
Thommes K, Lennartsson J, Carlberg M, Ronnstrand L (1999) 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 341(Pt 1):211–216
Tian Q, Frierson HF Jr, Krystal GW, Moskaluk CA (1999) Activating c-kit gene mutations in human germ cell tumors. Am J Pathol 154:1643–1647
Tiffany NM, Wersinger EM, Garzotto M, Beer TM (2004) Imatinib mesylate and zoledronic acid in androgen-independent prostate cancer. Urology 63:934–939
Todd JR, Becker TM, Kefford RF, Rizos H (2013) Secondary c-kit mutations confer acquired resistance to RTK inhibitors in c-kit mutant melanoma cells. Pigment Cell Melanoma Res 26:518–526
Tulina N, Matunis E (2001) Control of stem cell self-renewal in drosophila spermatogenesis by JAK-STAT signaling. Science 294:2546–2549
Verstraete K, Savvides SN (2012) Extracellular assembly and activation principles of oncogenic class III receptor tyrosine kinases. Nat Rev Cancer 12:753–766
Voytyuk O, Lennartsson J, Mogi A, Caruana G, Courtneidge S, Ashman LK, Ronnstrand L (2003) Src family kinases are involved in the differential signaling from two splice forms of c-kit. J Biol Chem 278:9159–9166
Wandzioch E, Edling CE, Palmer RH, Carlsson L, Hallberg B (2004) Activation of the MAP kinase pathway by c-kit is PI-3 kinase dependent in hematopoietic progenitor/stem cell lines. Blood 104:51–57
Weiler SR, Mou S, DeBerry CS, Keller JR, Ruscetti FW, Ferris DK, Longo DL, Linnekin D (1996) JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor. Blood 87:3688–3693
Williams DE, Eisenman J, Baird A, Rauch C, Van Ness K, March CJ, Park LS, Martin U, Mochizuki DY, Boswell HS, Burgess GS, Cosma D, Stewart DL (1990) Identification of a ligand for the c-kit proto-oncogene. Cell 63:167–174
Willmore-Payne C, Holden JA, Chadwick BE, Layfield LJ (2006) Detection of c-kit exons 11- and 17-activating mutations in testicular seminomas by high-resolution melting amplicon analysis. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 19:1164–1169
Wu P, Cao Z, Wu S (2016) New Progress of Epigenetic Biomarkers in Urological Cancer 2016:9864047
Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A (1987) Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J 6:3341–3351
Yun E-J, Lo UG, Hsieh J-T (2016) The evolving landscape of prostate cancer stem cell: therapeutic implications and future challenges. Asian Journal of Urology 3:203–210
Zhang Z, Zhang R, Joachimiak A, Schlessinger J, Kong XP (2000) Crystal structure of human stem cell factor: implication for stem cell factor receptor dimerization and activation. Proc Natl Acad Sci U S A 97:7732–7737
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12079-017-0399-1