PathwayStep4158 PathwayStep4157 PathwayStep4156 Tyrosine kinase inhibitors bind and inhibit overexpressed FGFR1 dimers Ligand-independent phosphorylation of overexpressed FGFR1 Ligand-independent dimerization of overexpressed FGFR1 Signaling by FGFR1 amplification mutants Amplification or activation of FGFR1 has been reported in lung cancer (Weiss, 2001; Marek, 2009; Dutt, 2011), breast cancer (Reis-Filho, 2006; Turner, 2010), oral squamous carcinoma (Freier, 2007), esophageal squamous cell carcinomas (Ishizuka, 2002), ovarian cancer (Gorringe, 2007), bladder cancer (Simon, 2001), prostate cancer (Edwards, 2003; Acevedo, 2007) and rhabodomyosarcoma (Missiaglia, 2009). Unlike the case for FGFR2 amplifications, FGFR1 amplifications are not associated with additional point mutations and affect signaling without altering the intrinsic kinase activity of the receptor. Overexpressed FGFR1 appears to signal at a basal level in a ligand-independent fashion, but is also able to be stimulated by exogenous ligand. Downstream activation may be the result of aberrant paracrine or autocrine stimulation (reviewed in Turner and Gross, 2010; Greulich and Pollock, 2011). FGFR1 amplification has not been conclusively demonstrated to be the causative oncogenic agent in all of the cancer types mentioned above, and other genes in the 8p11 region may also be candidates in some cases (Bass, 2009; Bernard-Pierrot, 2008; Ray, 2004). Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 Pubmed11389083 Pubmed12147242 Pubmed14614009 Pubmed14729606 Pubmed16807070 Pubmed17121884 Pubmed17699850 Pubmed18068632 Pubmed18757432 Pubmed18849352 Pubmed19235922 Pubmed19801978 Pubmed20094046 Pubmed20179196 Pubmed21160078 Pubmed21367659 Pubmed21666749 Reactome Database ID Release 431839120 Reactome, http://www.reactome.org ReactomeREACT_120827 Reviewed: Ezzat, S, 2012-05-15