Sarkar, Sourav, Ryan, Ellis L. and Royle, Stephen J. (2017) FGFR3–TACC3 cancer gene fusions cause mitotic defects by removal of endogenous TACC3 from the mitotic spindle. Open Biology, 7 (8). 170080. doi:10.1098/rsob.170080 ISSN 2046-2441.
Preview |
PDF
WRAP-FGFR3–TACC3-cancer-gene-fusions-cause-mitotic-defects-Royle-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1MB) | Preview |
Abstract
Fibroblast growth factor receptor 3–transforming acidic coiled-coil containing protein 3 (FGFR3–TACC3; FT3) is a gene fusion resulting from rearrangement of chromosome 4 that has been identified in many cancers including those of the urinary bladder. Altered FGFR3 signalling in FT3-positive cells is thought to contribute to cancer progression. However, potential changes in TACC3 function in these cells have not been explored. TACC3 is a mitotic spindle protein required for accurate chromosome segregation. Errors in segregation lead to aneuploidy, which can contribute to cancer progression. Here we show that FT3-positive bladder cancer cells have lower levels of endogenous TACC3 on the mitotic spindle, and that this is sufficient to cause mitotic defects. FT3 is not localized to the mitotic spindle, and by virtue of its TACC domain, recruits endogenous TACC3 away from the spindle. Knockdown of the fusion gene or low-level overexpression of TACC3 partially rescues the chromosome segregation defects in FT3-positive bladder cancer cells. This function of FT3 is specific to TACC3 as inhibition of FGFR3 signalling does not rescue the TACC3 level on the spindle in these cancer cells. Models of FT3-mediated carcinogenesis should, therefore, include altered mitotic functions of TACC3 as well as altered FGFR3 signalling.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
| Library of Congress Subject Headings (LCSH): | Bladder -- Cancer -- Research, Aneuploidy, Cell cycle |
| Journal or Publication Title: | Open Biology |
| Publisher: | The Royal Society Publishing |
| ISSN: | 2046-2441 |
| Official Date: | 30 August 2017 |
| Dates: | Date Event 30 August 2017 Available 22 July 2017 Accepted |
| Volume: | 7 |
| Number: | 8 |
| Article Number: | 170080 |
| DOI: | 10.1098/rsob.170080 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Open Access (Creative Commons open licence) |
| Date of first compliant deposit: | 2 October 2017 |
| Date of first compliant Open Access: | 3 October 2017 |
| Funder: | Cancer Research UK (CRUK) |
| Grant number: | C25425/A15182 |
| URI: | https://wrap.warwick.ac.uk/92822/ |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |