The paradox of FGFR3 signaling in skeletal dysplasia: Why chondrocytes growth arrest while other cells over proliferate
| Authors | |
|---|---|
| Year of publication | 2014 |
| Type | Article in Periodical |
| Magazine / Source | Mutation Research - Reviews in Mutation Research |
| MU Faculty or unit | |
| Citation | |
| Doi | http://dx.doi.org/10.1016/j.mrrev.2013.11.001 |
| Field | Biochemistry |
| Keywords | FGFR3; RASopathies; ERK; Achondroplasia; Skeletal dyplasia; Cancer |
| Description | 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. |
| Related projects: |