FGFR3-TACC3 is an oncogenic fusion protein in respiratory epithelium

Best, SA; Harapas, CR; Kersbergen, A; Rathi, V; Asselin-Labat, ML; Sutherland, KD

Author(s): Best, SA; Harapas, CR; Kersbergen, A; Rathi, V; Asselin-Labat, ML; Sutherland, KD;
Details: Publication Year 2018-11,Volume 37,Issue #46,Page 6096-6104
Journal Title: Oncogene
Publication Type: Journal Article
Abstract: Structural rearrangements of the genome can drive lung tumorigenesis through the generation of fusion genes with oncogenic properties. Advanced genomic approaches have identified the presence of a genetic fusion between fibroblast growth factor receptor 3 (FGFR3) and transforming acidic coiled-coil 3 (TACC3) in non-small cell lung cancer (NSCLC), providing a novel target for FGFR inhibition. To interrogate the functional consequences of the FGFR3-TACC3 fusion in the transformation of lung epithelial cells, we generated a novel transgenic mouse model that expresses FGFR3-TACC3 concomitant with loss of the p53 tumor suppressor gene. Intranasal delivery of an Ad5-CMV-Cre virus promoted seromucinous glandular transformation of olfactory cells lining the nasal cavities of FGFR3-TACC3 (LSL-F3T3) mice, which was further accelerated upon loss of p53 (LSL-F3T3/p53). Surprisingly, lung tumors failed to develop in intranasally infected LSL-F3T3 and LSL-F3T3/p53 mice. In line with these observations, we demonstrated that intranasal delivery of Ad5-CMV-Cre induces widespread Cre-mediated recombination in the olfactory epithelium. Intra-tracheal delivery of Ad5-CMV-Cre into the lungs of LSL-F3T3 and LSL-F3T3/p53 mice, however, resulted in the development of lung adenocarcinomas. Taken together, these findings provide in vivo evidence for an oncogenic function of FGFR3-TACC3 in respiratory epithelium.
Publisher: Springer Nature
Research Division(s): Stem Cells And Cancer
PubMed ID: 29991799
Link To PubMed Central Version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215478/
Publisher's Version: https://doi.org/10.1038/s41388-018-0399-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2018-07-23 09:32:16

Last Modified: 2019-03-14 11:42:06