The paradox of FGFR3 signaling in skeletal dysplasia: Why chondrocytes growth arrest while other cells over proliferate

KREJČÍ, Pavel. The paradox of FGFR3 signaling in skeletal dysplasia: Why chondrocytes growth arrest while other cells over proliferate. Mutation Research - Reviews in Mutation Research. Amsterdam: Elsevier Science, 2014, vol. 759, January–March, p. 40-48. ISSN 1383-5742. Available from: https://dx.doi.org/10.1016/j.mrrev.2013.11.001.

Basic information

• Original name: The paradox of FGFR3 signaling in skeletal dysplasia: Why chondrocytes growth arrest while other cells over proliferate
• Authors: KREJČÍ, Pavel (203 Czech Republic, guarantor, belonging to the institution).
• Edition: Mutation Research - Reviews in Mutation Research, Amsterdam, Elsevier Science, 2014, 1383-5742.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: Netherlands
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 6.213
• RIV identification code: RIV/00216224:14110/14:00073450
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1016/j.mrrev.2013.11.001
• UT WoS: 000333857600004
• Keywords in English: FGFR3; RASopathies; ERK; Achondroplasia; Skeletal dyplasia; Cancer
• Tags: EL OK
• Tags: International impact, Reviewed

Abstract

Somatic mutations in receptor tyrosine kinase FGFR3 cause excessive cell proliferation, leading to cancer or skin overgrowth. Remarkably, the same mutations inhibit chondrocyte proliferation and differentiation in developing bones, resulting in skeletal dysplasias, such as hypochondroplasia, achondroplasia, SADDAN and thanatophoric dysplasia. A similar phenotype is observed in Noonan syndrome, Leopard syndrome, hereditary gingival fibromatosis, neurofibromatosis type 1, Costello syndrome, Legius syndrome and cardiofaciocutaneous syndrome. Collectively termed RASopathies, the latter syndromes are caused by germline mutations in components of the RAS/ERK MAP kinase signaling pathway. This article considers the evidence suggesting that FGFR3 activation in chondrocytes mimics the activation of major oncogenes signaling via the ERK pathway. Subsequent inhibition of chondrocyte proliferation in FGFR3-related skeletal dysplasias and RASopathies is proposed to result from activation of defense mechanisms that originally evolved to safeguard mammalian organisms against cancer.

Links

• GAP305/11/0752, research and development project: Name: Molekulární základy FGFR3 signalingu v kostní dysplázii

Investor: Czech Science Foundation

• LH12004, research and development project: Name: FGFR3-specifický adaptérom a jeho role v patologické FGFR3 signalizaci v nemoci (Acronym: AMVIS-FGFR3)

Investor: Ministry of Education, Youth and Sports of the CR

• MUNI/M/0071/2013, interní kód MU: Name: High-throughput screening of compound libraries aimed on discovery of novel inhibitors of the FGFR/ERK MAP kinase signaling (Acronym: HTS-FGFR)

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects