Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by
Ectopic Signaling

J 2021

Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling

NITA, Alexandru, Sara POOVAKULATHU ABRAHAM, Pavel KREJČÍ a Michaela BOSÁKOVÁ

Základní údaje

Originální název

Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling

Autoři

NITA, Alexandru (642 Rumunsko, domácí), Sara POOVAKULATHU ABRAHAM (356 Indie, domácí), Pavel KREJČÍ (203 Česká republika, domácí) a Michaela BOSÁKOVÁ (203 Česká republika, garant, domácí)

Vydání

Cells, Basel, MDPI, 2021, 2073-4409

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.666

Kód RIV

RIV/00216224:14110/21:00122060

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3390/cells10061445

UT WoS

000667840600001

Klíčová slova anglicky

FGFR; fibroblast growth factor receptor; FGFR fusion; cancer; oncogenic driver; neoplastic transformation; primary cilia; cilia; centrosome; centrosome cycle

Štítky

14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 21. 2. 2022 13:13, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

EF19_073/0016943, projekt VaV

Název: Interní grantová agentura Masarykovy univerzity

MUNI/A/1325/2020, interní kód MU

Název: Biomedicínské vědy

Investor: Masarykova univerzita, Biomedicínské vědy

Citovat

NITA, Alexandru, Sara POOVAKULATHU ABRAHAM, Pavel KREJČÍ a Michaela BOSÁKOVÁ. Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling. Cells. Basel: MDPI, 2021, roč. 10, č. 6, s. 1-25. ISSN 2073-4409. Dostupné z: https://dx.doi.org/10.3390/cells10061445.

@article{1785577,
   author = {Nita, Alexandru and Poovakulathu Abraham, Sara and Krejčí, Pavel and Bosáková, Michaela},
   article_location = {Basel},
   article_number = {6},
   doi = {http://dx.doi.org/10.3390/cells10061445},
   keywords = {FGFR; fibroblast growth factor receptor; FGFR fusion; cancer; oncogenic driver; neoplastic transformation; primary cilia; cilia; centrosome; centrosome cycle},
   language = {eng},
   issn = {2073-4409},
   journal = {Cells},
   title = {Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling},
   url = {https://www.mdpi.com/2073-4409/10/6/1445},
   volume = {10},
   year = {2021}
}

TY  - JOUR
ID  - 1785577
AU  - Nita, Alexandru - Poovakulathu Abraham, Sara - Krejčí, Pavel - Bosáková, Michaela
PY  - 2021
TI  - Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling
JF  - Cells
VL  - 10
IS  - 6
SP  - 1-25
EP  - 1-25
PB  - MDPI
SN  - 20734409
KW  - FGFR
KW  - fibroblast growth factor receptor
KW  - FGFR fusion
KW  - cancer
KW  - oncogenic driver
KW  - neoplastic transformation
KW  - primary cilia
KW  - cilia
KW  - centrosome
KW  - centrosome cycle
UR  - https://www.mdpi.com/2073-4409/10/6/1445
N2  - 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.
ER  -

NITA, Alexandru, Sara POOVAKULATHU ABRAHAM, Pavel KREJČÍ a Michaela BOSÁKOVÁ. Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling. \textit{Cells}. Basel: MDPI, 2021, roč.~10, č.~6, s.~1-25. ISSN~2073-4409. Dostupné z: https://dx.doi.org/10.3390/cells10061445.

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