Environmental stresses induce karyotypic instability in colorectal cancer cells

Simple item page
dc.contributor.authorTan, Zhihaoen
dc.contributor.authorChan, Yong Jie Andrewen
dc.contributor.authorChua, Ying Jie Karenen
dc.contributor.authorRutledge, Samuel D.en
dc.contributor.authorPavelka, Normanen
dc.contributor.authorCimini, Danielaen
dc.contributor.authorRancati, Giuliaen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2019-08-30T17:00:08Zen
dc.date.available2019-08-30T17:00:08Zen
dc.date.issued2019-01en
dc.description.abstractUnderstanding how cells acquire genetic mutations is a fundamental biological question with implications for many different areas of biomedical research, ranging from tumor evolution to drug resistance. While karyotypic heterogeneity is a hallmark of cancer cells, few mutations causing chromosome instability have been identified in cancer genomes, suggesting a nongenetic origin of this phenomenon. We found that in vitro exposure of karyotypically stable human colorectal cancer cell lines to environmental stress conditions triggered a wide variety of chromosomal changes and karyotypic heterogeneity. At the molecular level, hyperthermia induced polyploidization by perturbing centrosome function, preventing chromosome segregation, and attenuating the spindle assembly checkpoint. The combination of these effects resulted in mitotic exit without chromosome segregation. Finally, heat- induced tetraploid cells were on the average more resistant to chemotherapeutic agents. Our studies suggest that environmental perturbations promote karyotypic heterogeneity and could contribute to the emergence of drug resistance.en
dc.description.notesWe thank the Rancati and Pavelka labs for helpful discussions, Mathijs Voorhoeve for the pBabe-H2B-GFP plasmid, Graham Wright and members of the IMB Microscopy Unit for their assistance and advice, and Anna De Antoni from the FIRC Institute of Molecular Oncology for the coimmunoprecipitation advice. This study was funded by an A*STAR Investigatorship (Ref. No. 1437a00119) awarded to G.R. Work in the Cimini lab was partly supported by National Science Foundation grant MCB-1517506.en
dc.description.sponsorshipA*STAR Investigatorship [1437a00119]; National Science Foundation [MCB-1517506]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1091/mbc.E18-10-0626en
dc.identifier.eissn1939-4586en
dc.identifier.issn1059-1524en
dc.identifier.issue1en
dc.identifier.pmid30379607en
dc.identifier.urihttp://hdl.handle.net/10919/93323en
dc.identifier.volume30en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.titleEnvironmental stresses induce karyotypic instability in colorectal cancer cellsen
dc.title.serialMolecular Biology of the Cellen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
mbc.e18-10-0626.pdf
Size:
7.43 MB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Scholarly Works, Biological Sciences
Scholarly Works, Fralin Life Sciences Institute