Alternative Splicing of Fibroblast Growth Factor Receptor IgIII Loops in Cancer.
Alternative splicing of the IgIII loop of fibroblast growth factor receptors (FGFRs) 1-3 produces b- and c-variants of the receptors with distinctly different biological impact based on their distinct ligand-binding spectrum. Tissue-specific expression of these splice variants regulates interactions in embryonic development, tissue maintenance and repair, and cancer. Alterations in FGFR2 splicing are involved in epithelial mesenchymal transition that produces invasive, metastatic features during tumor progression. Recent research has elucidated regulatory factors that determine the splice choice both on the level of exogenous signaling events and on the RNA-protein interaction level. Moreover, methodology has been developed that will enable the in depth analysis of splicing events during tumorigenesis and provide further insight on the role of FGFR 1-3 IIIb and IIIc in the pathophysiology of various malignancies. This paper aims to summarize expression patterns in various tumor types and outlines possibilities for further analysis and application.
Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
Klaus
K
Holzmann
Thomas
T
Grunt
Christine
C
Heinzle
Sandra
S
Sampl
Heinrich
H
Steinhoff
Nicole
N
Reichmann
Miriam
M
Kleiter
Marlene
M
Hauck
Brigitte
B
Marian