Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type-and mutation-specific manner

Oncogene

Volumn 28, Issue 48, 2009, Pages 4306-4316

  Di Martino, E ^a   L'Hte C G ^a   Kennedy, W ^a   Tomlinson, D C ^a   Knowles, M A ^a  

^a ST JAMES S UNIVERSITY HOSPITAL   (United Kingdom)

Author keywords

Bladder; FGFR3; Fibroblast growth factor; Signaling; Urothelium

Indexed keywords

FIBROBLAST GROWTH FACTOR RECEPTOR 3; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN KINASE B; PROTEIN MCL 1;

ANCHORAGE INDEPENDENT GROWTH; ANIMAL CELL; ANIMAL CELL CULTURE; ARTICLE; CELL DENSITY; CELL PROLIFERATION; CELL STRAIN 3T3; CELL TRANSFORMATION; CELL TYPE; CELL VIABILITY; CONTROLLED STUDY; ENZYME PHOSPHORYLATION; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IN VITRO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; UROTHELIUM;

AMINO ACID SUBSTITUTION; ANIMALS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; HUMANS; MALE; MAP KINASE SIGNALING SYSTEM; MICE; MUTATION; PHOSPHORYLATION; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 3; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TRANSFECTION; URINARY BLADDER NEOPLASMS; UROTHELIUM;

EID: 71349085679     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2009.280     Document Type: Article

References (46)

1. Adar R, Monsonego-Ornan E, David P, Yayon A. (2002). Differential activation of cysteine-substitution mutants of fibroblast growth factor receptor 3 is determined by cysteine localization. J Bone Miner Res 17: 860-868.
2. Agazie YM, Movilla N, Ischenko I, Hayman MJ. (2003). The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3. Oncogene 22: 6909-6918.
3. Bernard-Pierrot I, Brams A, Dunois-Larde C, Caillault A, Diez de Medina SG, Cappellen D et al. (2006). Oncogenic properties of the mutated forms of fibroblast growth factor receptor 3b. Carcino-genesis 27: 740-747.
4. Bonaventure J, Horne WC, Baron R. (2007). The localization of FGFR3 mutations causing thanatophoric dysplasia type I differentially affects phosphorylation, processing and ubiquitylation of the receptor. FEBS J 274: 3078-3093.
5. Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X et al. (1999). Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 23: 18-20.
6. Chapman EJ, Hurst CD, Pitt E, Chambers P, Aveyard JS, Knowles MA. (2006). Expression of hTERT immortalises normal human urothelial cells without inactivation of the p16/Rb pathway. Oncogene 25: 5037-5045.
7. Chen J, Williams IR, Lee BH, Duclos N, Huntly BJ, Donoghue DJ et al. (2005). Constitutively activated FGFR3 mutants signal through PLCgamma-dependent and-independent pathways for hematopoietic transformation. Blood 106: 328-337.
8. Chen L, Adar R, Yang X, Monsonego EO, Li C, Hauschka PV et al. (1999). Gly369Cys mutation in mouse FGFR3 causes achondro-plasia by affecting both chondrogenesis and osteogenesis. J Clin Invest 104: 1517-1525.
9. Chesi M, Brents LA, Ely SA, Bais C, Robbiani DF, Mesri EA et al. (2001). Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma. Blood 97: 729-736
10. d'Avis PY, Robertson SC, Meyer AN, Bardwell WM, Webster MK, Donoghue DJ. (1998). Constitutive activation of fibroblast growth factor receptor 3 by mutations responsible for the lethal skeletal dysplasia thanatophoric dysplasia type I. Cell Growth Differ 9: 71-78.
11. Dailey L, Ambrosetti D, Mansukhani A, Basilico C. (2005). Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev 16: 233-247.
12. Eswarakumar VP, Lax I, Schlessinger J. (2005). Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 16: 139-149.
13. Garcia-Espana A, Salazar E, Sun TT, Wu XR, Pellicer A. (2005). Differential expression of cell cycle regulators in phenotypic variants of transgenically induced bladder tumors: implications for tumor behavior. Cancer Res 65: 1150-1157.
14. Gibbs L, Legeai-Mallet L. (2007). FGFR3 intracellular mutations induce tyrosine phosphorylation in the Golgi and defective glycosylation. Biochim Biophys Acta 1773: 502-512.
15. Guy M, Moorghen M, Bond JA, Collard TJ, Paraskeva C, Williams AC. (2001). Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells. Br J Cancer 84: 520-528.
16. Hafner C, Vogt T, Hartmann A. (2006). FGFR3 mutations in benign skin tumors. Cell Cycle 5: 2723-2728.
17. Harada D, Yamanaka Y, Ueda K, Nishimura R, Morishima T, Seino Y et al. (2007). Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via PLCgamma-activated STAT1. Bone 41: 273-281.
18. Harbour JW, Dean DC. (2000). Rb function in cell-cycle regulation and apoptosis. Nat Cell Biol 2: E65-E67.
19. Hart KC, Robertson SC, Donoghue DJ. (2001). Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, Stat activation, and phospha-tidylinositol 3-kinase activation. Mol Biol Cell 12: 931-942.
20. Karoui M, Hofmann-Radvanyi H, Zimmermann U, Couvelard A, Degott C, Faridoni-Laurens L et al. (2001). No evidence of somatic FGFR3 mutation in various types of carcinoma. Oncogene 20: 5059-5061.
21. Korkolopoulou P, Lazaris A, Konstantinidou AE, Kavantzas N, Patsouris E, Christodoulou P et al. (2002). Differential expression of bcl-2 family proteins in bladder carcinomas. Relationship with apoptotic rate and survival. Eur Urol 41: 274-283.
22. Legeai-Mallet L, Benoist-Lasselin C, Munnich A, Bonaventure J. (2004). Overexpression of FGFR3, Stat1, Stat5 and p21Cip1 correlates with phenotypic severity and defective chondrocyte differentiation in FGFR3-related chondrodysplasias. Bone 34: 26-36.
23. Li C, Chen L, Iwata T, Kitagawa M, Fu XY, Deng CX. (1999). A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors. Hum Mol Genet 8: 35-44.
24. Lievens PM, Liboi E. (2003). The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum. J Biol Chem 278: 17344-17349.
25. Lievens PM, Roncador A, Liboi E. (2006). K644E/M FGFR3 mutants activate Erk1/2 from the endoplasmic reticulum through FRS2alpha and PLCgamma-independent pathways. J Mol Biol 357: 783-792.
26. Martinez-Torrecuadrada J, Cifuentes G, Lopez-Serra P, Saenz P, Martinez A, Casal JI. (2005). Targeting the extracellular domain of fibroblast growth factor receptor 3 with human single-chain Fv antibodies inhibits bladder carcinoma cell line proliferation. Clin Cancer Res 11: 6280-6290.
27. Monsonego-Ornan E, Adar R, Rom E, Yayon A. (2002). FGF receptors ubiquitylation: dependence on tyrosine kinase activity and role in downregulation. FEBS Lett 528: 83-89.
28. Murakami M, Elfenbein A, Simons M. (2008). Non-canonical fibroblast growth factor signalling in angiogenesis. Cardiovasc Res 78: 223-231.
29. Naski MC, Wang Q, Xu J, Ornitz DM. (1996). Graded activation of fibroblast growth factor receptor 3 by mutations causing achon-droplasia and thanatophoric dysplasia. Nat Genet 13: 233-237.
30. Ornitz DM, Itoh N. (2001). Fibroblast growth factors. Genome Biol 2: REVIEWS3005.
31. Ronchetti D, Greco A, Compasso S, Colombo G, Dell'Era P, Otsuki T et al. (2001). Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations. Oncogene 20: 3553-3562.
32. Sahni M, Ambrosetti DC, Mansukhani A, Gertner R, Levy D, Basilico C. (1999). FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway. Genes Dev 13: 1361-1366.
33. Santamaria D, Barriere C, Cerqueira A, Hunt S, Tardy C, Newton K et al. (2007). Cdk1 is sufficient to drive the mammalian cell cycle. Nature 448: 811-815.
34. Sibley K, Cuthbert-Heavens D, Knowles MA. (2001a). Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma. Oncogene 20: 686-691.
35. Sibley K, Stern P, Knowles MA. (2001b). Frequency of fibroblast growth factor receptor 3 mutations in sporadic tumours. Oncogene 20: 4416-4418.
36. Su WC, Kitagawa M, Xue N, Xie B, Garofalo S, Cho J et al. (1997). Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism. Nature 386: 288-292.
37. Tomlinson DC, Baldo O, Harnden P, Knowles MA. (2007a). FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol 213: 91-98.
38. Tomlinson DC, Hurst CD, Knowles MA. (2007b). Knockdown by shRNA identifies S249C mutant FGFR3 as a potential therapeutic target in bladder cancer. Oncogene 26: 5889-5899.
39. Tomlinson DC, L'Hote CG, Kennedy W, Pitt E, Knowles MA. (2005). Alternative splicing of fibroblast growth factor receptor 3 produces a secreted isoform that inhibits fibroblast growth factor-induced proliferation and is repressed in urothelial carcinoma cell lines. Cancer Res 65: 10441-10449.
40. van Oers JM, Adam C, Denzinger S, Stoehr R, Bertz S, Zaak D et al. (2006). Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial hyperplasias of the bladder. Int J Cancer 119: 1212-1215.
41. van Rhijn BW, van Tilborg AA, Lurkin I, Bonaventure J, de Vries A, Thiery JP et al. (2002). Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. Eur J Hum Genet 10: 819-824.
42. Wallerand H, Bakkar AA, de Medina SG, Pairon JC, Yang YC, Vordos D et al. (2005). Mutations in TP53, but not FGFR3, in urothelial cell carcinoma of the bladder are influenced by smoking: contribution of exogenous versus endogenous carcinogens. Carcino-genesis 26: 177-184.
43. Webster MK, D'Avis PY, Robertson SC, Donoghue DJ. (1996). Profound ligand-independent kinase activation of fibroblast growth factor receptor 3 by the activation loop mutation responsible for a lethal skeletal dysplasia, thanatophoric dysplasia type II. Mol Cell Biol 16: 4081-4087.
44. Webster MK, Donoghue DJ. (1997). Enhanced signaling and morphological transformation by a membrane-localized derivative of the fibroblast growth factor receptor 3 kinase domain. Mol Cell Biol 17: 5739-5747.
45. Wells A, Grandis JR. (2003). Phospholipase C-gamma1 in tumor progression. Clin Exp Metastasis 20: 285-290.
46. Yamamoto H, Monden T, Ikeda K, Izawa H, Fukuda K, Fukunaga M et al. (1995). Coexpression of cdk2/cdc2 and retinoblastoma gene products in colorectal cancer. Br J Cancer 71: 1231-1236