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 and Michaela BOSÁKOVÁ

Basic information

Original name

Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling

Authors

NITA, Alexandru (642 Romania, belonging to the institution), Sara POOVAKULATHU ABRAHAM (356 India, belonging to the institution), Pavel KREJČÍ (203 Czech Republic, belonging to the institution) and Michaela BOSÁKOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cells, Basel, MDPI, 2021, 2073-4409

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.666

RIV identification code

RIV/00216224:14110/21:00122060

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000667840600001

Keywords in English

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

Abstract

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.

Links

EF19_073/0016943, research and development project

Name: Interní grantová agentura Masarykovy univerzity

MUNI/A/1325/2020, interní kód MU

Name: Biomedicínské vědy

Investor: Masaryk University

Citovat

NITA, Alexandru, Sara POOVAKULATHU ABRAHAM, Pavel KREJČÍ and Michaela BOSÁKOVÁ. Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling. Cells. Basel: MDPI, 2021, vol. 10, No 6, p. 1-25. ISSN 2073-4409. Available from: 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 and Michaela BOSÁKOVÁ. Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling. \textit{Cells}. Basel: MDPI, 2021, vol.~10, No~6, p.~1-25. ISSN~2073-4409. Available from: https://dx.doi.org/10.3390/cells10061445.

Detailed Information on Publication Record