To screen candidate molecules that might be useful as diagnostic
biomarkers or for development of novel molecular-targeting
therapies, we previously carried out gene-expression profile analysis of 101 lung
carcinomas and detected an elevated expression of FGFR1OP (
fibroblast growth factor receptor 1 oncogene partner) in the majority of
lung cancers. Immunohistochemical staining using
tumor tissue microarrays consisting of 372 archived
non-small cell lung cancer (NSCLC) specimens revealed positive staining of FGFR1OP in 334 (89.8%) of 372 NSCLCs. We also found that the high level of FGFR1OP expression was significantly associated with shorter
tumor-specific survival times (P < 0.0001 by log-rank test). Moreover, multivariate analysis determined that FGFR1OP was an independent prognostic factor for surgically treated NSCLC patients (P < 0.0001). Treatment of
lung cancer cells, in which endogenous FGFR1OP was overexpressed, using FGFR1OP
siRNA, suppressed its expression and resulted in inhibition of the cell growth. Furthermore, induction of FGFR1OP increased the cellular motility and growth-promoting activity of mammalian cells. To investigate its function, we searched for FGFR1OP-interacting
proteins in
lung cancer cells and identified ABL1 (Abelson murine
leukemia viral oncogene homolog 1) and WRNIP1 (Werner helicase interacting
protein 1), which was known to be involved in cell cycle progression. FGFR1OP significantly reduced ABL1-dependent phosphorylation of WRNIP1 and resulted in the promotion of cell cycle progression. Because our data imply that FGFR1OP is likely to play a significant role in
lung cancer growth and progression, FGFR1OP should be useful as a prognostic
biomarker and probably as a therapeutic target for
lung cancer.