Dimerization of overexpressed FGFR2

Stable Identifier
Reaction [transition]
Homo sapiens
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Overexpressed FGFR2 in gastric and breast cancer cells has been shown to undergo ligand-independent dimerization (Takeda, 2007; Kunii, 2008; Moffa, 2004; Turner, 2010). Full-length FGFR2 is weakly transforming in NIH 3T3 cells, and is thought to possess a transformation-inhibiting domain in the C-terminus (Itoh, 1994). Interestingly, many cancers with amplifications of FGFR2 show preferrential expression of C-terminally truncated FGFR2 variants, designated C2 and C3, with 788 or 769 residues instead of the wild-type 822 (Hattori, 1990; Itoh, 1994; Ueda, 1999). These variants, which lack a number of carboxy-terminal tyrosine residues, show increased transforming potency compared to the full-length receptor (Cha, 2008; Cha, 2009), and have been shown to be constitutively active and to dimerize spontaneously (Takeda, 2007).
Literature References
PubMed ID Title Journal Year
10626794 Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short homology-mediated recombination, generating preferential expression of specific messenger RNAs

Sakamoto, H, Shibuya, T, Kuwahara, Y, Yanagihara, K, Nezu, M, Ishii, H, Sasaki, H, Terada, M, Makuuchi, M, Ueda, T, Mafune, K

Cancer Res 1999
18337450 Involvement of fibroblast growth factor receptor 2 isoform switching in mammary oncogenesis

Der, CJ, Cha, JY, Lambert, QT, Reuther, GW

Mol Cancer Res 2008
17505008 AZD2171 shows potent antitumor activity against gastric cancer over-expressing fibroblast growth factor receptor 2/keratinocyte growth factor receptor

Fukuoka, K, Yamada, Y, Yanagihara, K, Nishio, K, Sasaki, H, Kimura, H, Takeda, M, Tamura, T, Komatsu, T, Yokote, H, Arao, T, Saijo, N

Clin Cancer Res 2007
2377625 K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes

Sakamoto, H, Odagiri, H, Miyagawa, K, Sugimura, T, Katoh, O, Yoshida, T, Naito, K, Hattori, Y, Terada, M, Nakatani, H

Proc Natl Acad Sci U S A 1990
15561780 Transforming potential of alternatively spliced variants of fibroblast growth factor receptor 2 in human mammary epithelial cells

Moffa, AB, Ethier, SP, Tannheimer, SL

Mol Cancer Res 2004
20101236 Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets

Geyer, FC, van Kouwenhove, M, van de Vijver, MJ, Horlings, HM, Reis-Filho, JS, Ashworth, A, Lambros, MB, Natrajan, R, Sharpe, R, Turner, N, Kreike, B, Mackay, A, Pearson, A

Oncogene 2010
19103595 Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform

Der, CJ, Harden, TK, Mitin, N, Cha, JY, Maddileti, S

J Biol Chem 2009
8205545 Preferential alternative splicing in cancer generates a K-sam messenger RNA with higher transforming activity

Sakamoto, H, Kishi, T, Koono, M, Itoh, H, Ishii, H, Sasaki, H, Sugimura, T, Yoshida, T, Hattori, Y, Terada, M

Cancer Res 1994
18381441 FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival

Kunii, K, Gorenstein, J, Hatch, H, Lutterbach, B, Yashiro, M, Davis, L, Di Bacco, A, Elbi, C

Cancer Res 2008
Functional status

Gain of function of Overexpressed FGFR2 [plasma membrane]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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