Reactome: A Curated Pathway Database

Signaling by FGFR2 amplification mutants (R-HSA-2023837)

Species Homo sapiens


FGFR2 amplifications have been identified in 10% of gastric cancers, where they are associated with poor prognosis diffuse cancers (Hattori, 1996; Ueda, 1999; Shin, 2000; Kunii, 2008) , and in ~1% of breast cancers (Turner, 2010; Tannheimer, 2000). FGFR2 amplification often occur in conjunction with deletions of C-terminal exons, resulting in expression of a internalization- and degradation-resistant form of the receptor (Takeda, 1999; Cha, 2008, 2009). Amplification affects signaling without altering the intrinsic kinase activity of the receptor. Signaling through overexpressed FGFR2 also shows evidence of being ligand-independent and sensitive to FGFR inhibitors (Lorenzi, 1997; Takeda, 1999; Cha, 2009).

Locations in the PathwayBrowser
Additional Information
Compartment nucleoplasm , plasma membrane
Name Identifier Synonyms
cancer 162 [malignant tumor, malignant neoplasm, primary cancer]
Literature References
pubMedId Title Journal Year
17505008 AZD2171 shows potent antitumor activity against gastric cancer over-expressing fibroblast growth factor receptor 2/keratinocyte growth factor receptor Clin Cancer Res 2007
20101236 Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets Oncogene 2010
18381441 FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival Cancer Res 2008
19103595 Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform J Biol Chem 2009
10626794 Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short homology-mediated recombination, generating preferential expression of specific messenger RNAs Cancer Res 1999
9816310 Immunohistochemical detection of K-sam protein in stomach cancer Clin Cancer Res 1996
9266968 Ligand-independent activation of fibroblast growth factor receptor-2 by carboxyl terminal alterations Oncogene 1997
11056689 Characterization of fibroblast growth factor receptor 2 overexpression in the human breast cancer cell line SUM-52PE Breast Cancer Res 2000
18337450 Involvement of fibroblast growth factor receptor 2 isoform switching in mammary oncogenesis Mol Cancer Res 2008
11003564 Up-regulation and co-expression of fibroblast growth factor receptors in human gastric cancer J Cancer Res Clin Oncol 2000