Targets of fibroblast growth factor 1 (FGF-1) and FGF-2 signaling involved in the invasive and tumorigenic behavior of carcinoma cells

被引:36
作者
Billottet, C [1 ]
Elkhatib, N [1 ]
Thiery, JP [1 ]
Jouanneau, J [1 ]
机构
[1] Inst Curie, Sect Rech, CNRS, UMR144,Lab Cell Morphogenesis & Tumor Progress, F-75248 Paris 05, France
关键词
D O I
10.1091/mbc.E04-04-0336
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Fibroblast growth factor (FGF)-1 and -2 have potent biological activities implicated in malignant tumor development. Their autocrine and nonautocrine activity in tumor progression of carcinoma was investigated in the NBT-II cell system. Cells were manipulated to either produce and be autocrine for FGF-1 or -2 or to only produce but not respond to these factors. The autocrine cells are highly invasive and tumorigenic and the determination of specific targets of FGF/fibroblast growth factor receptor (FGFR) signaling was assessed. In vitro studies showed that nonautocrine cells behave like epithelial parental cells, whereas autocrine cells have a mesenchymal phenotype correlated with the overexpression of urokinase plasminogen activator receptor (uPAR), the internalization of E-cadherin, and the redistribution of beta-catenin from the cell surface to the cytoplasm and nucleus. uPAR was defined as an early target, whereas E-cadherin and the leukocyte common antigen-related protein-tyrosine phosphatase (LAR-PTP) were later targets of FGF signaling, with FGFR1 activation more efficient than FGFR2 at modulating these targets. Behavior of autocrine cells was consistent with a decrease of tumor-suppressive activities of both E-cadherin and LAR-PTP. These molecular analyses show that the potential of these two growth factors in tumor progression is highly dependent on specific FGFR signaling and highlights its importance as a target for antitumor therapy.
引用
收藏
页码:4725 / 4734
页数:10
相关论文
共 47 条
[1]   Oncogenic transformation by β-catenin:: deletion analysis and characterization of selected target genes [J].
Aoki, M ;
Sobek, V ;
Maslyar, DJ ;
Hecht, A ;
Vogt, PK .
ONCOGENE, 2002, 21 (46) :6983-6991
[2]   Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo [J].
Ardini, E ;
Agresti, R ;
Tagliabue, E ;
Greco, M ;
Aiello, P ;
Yang, LT ;
Ménard, S ;
Sap, J .
ONCOGENE, 2000, 19 (43) :4979-4987
[3]  
Behrens J, 2000, ANN NY ACAD SCI, V910, P21
[4]   Receptor protein tyrosine phosphatases as mediators of cellular adhesion [J].
Beltran, PJ ;
Bixby, JL .
FRONTIERS IN BIOSCIENCE, 2003, 8 :D87-D99
[5]   Rapid tumor development and potent vascularization are independent events in carcinoma producing FGF-1 or FGF-2 [J].
Billottet, C ;
Janji, B ;
Thiery, JP ;
Jouanneau, J .
ONCOGENE, 2002, 21 (53) :8128-8139
[6]   uPAR: A versatile signalling orchestrator [J].
Blasi, F ;
Carmeliet, P .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (12) :932-943
[7]   Oncogenic kinase signalling [J].
Blume-Jensen, P ;
Hunter, T .
NATURE, 2001, 411 (6835) :355-365
[8]   Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1) [J].
Borgfeldt, C ;
Hansson, SR ;
Gustavsson, B ;
Måsbäck, A ;
Casslén, B .
INTERNATIONAL JOURNAL OF CANCER, 2001, 92 (04) :497-502
[9]  
Chandler LA, 1999, INT J CANCER, V81, P451, DOI 10.1002/(SICI)1097-0215(19990505)81:3<451::AID-IJC20>3.3.CO
[10]  
2-8