Differential effects of polymorphic alleles of FGF receptor 4 on colon cancer growth and metastasis

Christine Heinzle, Andrea Gsur, Monika Hunjadi, Zeynep Erdem, Christine Gauglhofer, Stefan Staẗtner, J. Karner, Martin Klimpfinger, Friedrich Wrba, Andrea Reti, B. Hegedűs, Andreas Baierl, Bettina Grasl-Kraupp, Klaus Holzmann, Michael Grusch, Walter Berger, Brigitte Marian

Research output: Contribution to journalArticle

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Abstract

A gly388arg polymorphism (rs351855) in the transmembrane domain of the fibroblast growth factor receptor (FGFR4) is associated with increased risk, staging, and metastasis in several different types of cancer. To specifically assess the impact of the polymorphic FGFR4 in colorectal cancer (CRC), we engineered CRC cell lines with distinct endogenous expression patterns to overexpress either the FGFR4gly or FGFR4arg alleles. The biologic analyses revealed an oncogenic importance for both polymorphic alleles, but FGFR4gly was the stronger inducer of tumor growth, whereas FGFR4arg was the stronger inducer of migration. An evaluation of clinical specimens revealed that FGFR4 was upregulated in 20/71 patients independent of gly388arg status. There was no correlation between the presence of an FGFR4arg allele and CRC or polyp risk in 3,471 participants of the CORSA study. However, among 182 patients with CRC, FGFR4arg-carriers had a fivefold higher risk of tumors that were stage II or greater. Together, our results established that both allelic forms of FGFR4 exert an oncogenic impact and may serve equally well as therapeutic targets in CRC. One important implication of our findings is that FGFR4 arg-carriers are at a higher risk for more aggressive tumors and therefore may profit from early detection measures.

Original languageEnglish
Pages (from-to)5767-5777
Number of pages11
JournalCancer Research
Volume72
Issue number22
DOIs
Publication statusPublished - Nov 15 2012

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Fibroblast Growth Factor Receptors
Colonic Neoplasms
Colorectal Neoplasms
Alleles
Neoplasm Metastasis
Growth
Neoplasms
Polyps
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Heinzle, C., Gsur, A., Hunjadi, M., Erdem, Z., Gauglhofer, C., Staẗtner, S., ... Marian, B. (2012). Differential effects of polymorphic alleles of FGF receptor 4 on colon cancer growth and metastasis. Cancer Research, 72(22), 5767-5777. https://doi.org/10.1158/0008-5472.CAN-11-3654

Differential effects of polymorphic alleles of FGF receptor 4 on colon cancer growth and metastasis. / Heinzle, Christine; Gsur, Andrea; Hunjadi, Monika; Erdem, Zeynep; Gauglhofer, Christine; Staẗtner, Stefan; Karner, J.; Klimpfinger, Martin; Wrba, Friedrich; Reti, Andrea; Hegedűs, B.; Baierl, Andreas; Grasl-Kraupp, Bettina; Holzmann, Klaus; Grusch, Michael; Berger, Walter; Marian, Brigitte.

In: Cancer Research, Vol. 72, No. 22, 15.11.2012, p. 5767-5777.

Research output: Contribution to journalArticle

Heinzle, C, Gsur, A, Hunjadi, M, Erdem, Z, Gauglhofer, C, Staẗtner, S, Karner, J, Klimpfinger, M, Wrba, F, Reti, A, Hegedűs, B, Baierl, A, Grasl-Kraupp, B, Holzmann, K, Grusch, M, Berger, W & Marian, B 2012, 'Differential effects of polymorphic alleles of FGF receptor 4 on colon cancer growth and metastasis', Cancer Research, vol. 72, no. 22, pp. 5767-5777. https://doi.org/10.1158/0008-5472.CAN-11-3654
Heinzle C, Gsur A, Hunjadi M, Erdem Z, Gauglhofer C, Staẗtner S et al. Differential effects of polymorphic alleles of FGF receptor 4 on colon cancer growth and metastasis. Cancer Research. 2012 Nov 15;72(22):5767-5777. https://doi.org/10.1158/0008-5472.CAN-11-3654
Heinzle, Christine ; Gsur, Andrea ; Hunjadi, Monika ; Erdem, Zeynep ; Gauglhofer, Christine ; Staẗtner, Stefan ; Karner, J. ; Klimpfinger, Martin ; Wrba, Friedrich ; Reti, Andrea ; Hegedűs, B. ; Baierl, Andreas ; Grasl-Kraupp, Bettina ; Holzmann, Klaus ; Grusch, Michael ; Berger, Walter ; Marian, Brigitte. / Differential effects of polymorphic alleles of FGF receptor 4 on colon cancer growth and metastasis. In: Cancer Research. 2012 ; Vol. 72, No. 22. pp. 5767-5777.
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