Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Chromosomally unstable tumor cells specifically require KIF18A for proliferation

Carolyn Marquis, Cindy L. Fonseca, Lisa Wood, Heidi L.H. Malaby, Joseph E. Clayton, View ORCID ProfileJason Stumpff
doi: https://doi.org/10.1101/2020.06.18.159327
Carolyn Marquis
1Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cindy L. Fonseca
1Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa Wood
1Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heidi L.H. Malaby
1Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph E. Clayton
2BioTek Instruments Inc., Winooski, VT 05404, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason Stumpff
1Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jason Stumpff
  • For correspondence: jstumpff@uvm.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Summary

Chromosomal instability (CIN), characterized by frequent missegregation of chromosomes during mitosis, is a hallmark of tumor cells caused by changes in the dynamics and control of microtubules that comprise the mitotic spindle1–3. Thus, CIN tumor cells may respond differently than normal diploid cells to treatments that target mitotic spindle regulation. We tested this idea by inhibiting a subset of kinesin motor proteins that control spindle microtubule dynamics and mechanics but are not required for the proliferation of near-diploid cells. Our results indicate that KIF18A is required for proliferation of CIN cells derived from triple negative breast cancer or colorectal cancer tumors but not normal breast epithelial cells or near-diploid colorectal cancer cells exhibiting microsatellite instability. CIN tumor cells exhibit mitotic delays, multipolar spindles due to centrosome fragmentation, and increased cell death following inhibition of KIF18A. These mitotic defects were further enhanced by increasing the activity of the microtubule depolymerizing kinesin KIF2C/MCAK and are reminiscent of the phenotypes that result from clinically relevant doses of the chemotherapeutic drug paclitaxel4. Our results indicate that the altered spindle microtubule dynamics characteristic of CIN tumor cells can be exploited to reduce their proliferative capacity.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted June 18, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Chromosomally unstable tumor cells specifically require KIF18A for proliferation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Chromosomally unstable tumor cells specifically require KIF18A for proliferation
Carolyn Marquis, Cindy L. Fonseca, Lisa Wood, Heidi L.H. Malaby, Joseph E. Clayton, Jason Stumpff
bioRxiv 2020.06.18.159327; doi: https://doi.org/10.1101/2020.06.18.159327
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Chromosomally unstable tumor cells specifically require KIF18A for proliferation
Carolyn Marquis, Cindy L. Fonseca, Lisa Wood, Heidi L.H. Malaby, Joseph E. Clayton, Jason Stumpff
bioRxiv 2020.06.18.159327; doi: https://doi.org/10.1101/2020.06.18.159327

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3482)
  • Biochemistry (7329)
  • Bioengineering (5301)
  • Bioinformatics (20212)
  • Biophysics (9985)
  • Cancer Biology (7706)
  • Cell Biology (11273)
  • Clinical Trials (138)
  • Developmental Biology (6425)
  • Ecology (9923)
  • Epidemiology (2065)
  • Evolutionary Biology (13292)
  • Genetics (9353)
  • Genomics (12559)
  • Immunology (7681)
  • Microbiology (18964)
  • Molecular Biology (7421)
  • Neuroscience (40915)
  • Paleontology (298)
  • Pathology (1226)
  • Pharmacology and Toxicology (2130)
  • Physiology (3145)
  • Plant Biology (6842)
  • Scientific Communication and Education (1271)
  • Synthetic Biology (1893)
  • Systems Biology (5299)
  • Zoology (1086)