Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling

0544015 - ÚŽFG 2022 RIV CH eng J - Journal Article
Nita, A. - Abraham, S. P. - Krejčí, Pavel - Bosáková, Michaela
Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling.
Cells. Roč. 10, č. 6 (2021), č. článku 1445. E-ISSN 2073-4409
R&D Projects: GA MŠMT(CZ) LTAUSA19030
Institutional support: RVO:67985904
Keywords : FGFR * fibroblast growth factor receptor * FGFR fusion
OECD category: Genetics and heredity (medical genetics to be 3)
Impact factor: 7.666, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2073-4409/10/6/1445

A single primary cilium projects from most vertebrate cells to guide cell fate decisions. A growing list of signaling molecules is found to function through cilia and control ciliogenesis, including the fibroblast growth factor receptors (FGFR). Aberrant FGFR activity produces abnormal cilia with deregulated signaling, which contributes to pathogenesis of the FGFR-mediated genetic disorders. FGFR lesions are also found in cancer, raising a possibility of cilia involvement in the neoplastic transformation and tumor progression. Here, we focus on FGFR gene fusions, and discuss the possible mechanisms by which they function as oncogenic drivers. We show that a substantial portion of the FGFR fusion partners are proteins associated with the centrosome cycle, including organization of the mitotic spindle and ciliogenesis. The functions of centrosome proteins are often lost with the gene fusion, leading to haploinsufficiency that induces cilia loss and deregulated cell division. We speculate that this complements the ectopic FGFR activity and drives the FGFR fusion cancers.
Permanent Link: http://hdl.handle.net/11104/0321080