Transient endoreplication down-regulates the kinesin-14 HSET and contributes to genomic instability

Shengyao Chen, Jane R. Stout, Sathiya Dharmaiah, Sarah Yde, Brian R. Calvi, Claire Walczak

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Polyploid cancer cells exhibit chromosomal instability (CIN), which is associated with tumorigenesis and therapy resistance. The mechanisms that induce polyploidy and how these mechanisms contribute to CIN are not fully understood. Here we evaluate CIN in human cells that become polyploid through an experimentally induced endoreplication cycle. When these induced endoreplicating cells (iECs) returned to mitosis, it resulted in aneuploidy in daughter cells. This aneuploidy resulted from multipolar divisions, chromosome missegregation, and failure in cytokinesis. The iECs went through several rounds of division, ultimately spawning proliferative cells of reduced ploidy. iECs have reduced levels of the kinesin-14 HSET, which likely accounts for the multipolar divisions, and overexpression of HSET reduced spindle multipolarity. However, HSET overexpression had only mild effects on CIN, suggesting that additional defects must contribute to genomic instability in dividing iECs. Overall our results suggest that transient endoreplication cycles generate a diverse population of proliferative aneuploid cells that have the potential to contribute to tumor heterogeneity.

Original languageEnglish (US)
Pages (from-to)2911-2923
Number of pages13
JournalMolecular Biology of the Cell
Volume27
Issue number19
DOIs
StatePublished - Oct 1 2016

Fingerprint

Endoreduplication
Kinesin
Genomic Instability
Chromosomal Instability
Down-Regulation
Polyploidy
Aneuploidy
Cytokinesis
Ploidies
Mitosis
Neoplasms
Carcinogenesis
Chromosomes
Population

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Transient endoreplication down-regulates the kinesin-14 HSET and contributes to genomic instability. / Chen, Shengyao; Stout, Jane R.; Dharmaiah, Sathiya; Yde, Sarah; Calvi, Brian R.; Walczak, Claire.

In: Molecular Biology of the Cell, Vol. 27, No. 19, 01.10.2016, p. 2911-2923.

Research output: Contribution to journalArticle

Chen, Shengyao ; Stout, Jane R. ; Dharmaiah, Sathiya ; Yde, Sarah ; Calvi, Brian R. ; Walczak, Claire. / Transient endoreplication down-regulates the kinesin-14 HSET and contributes to genomic instability. In: Molecular Biology of the Cell. 2016 ; Vol. 27, No. 19. pp. 2911-2923.
@article{11df8df12ff1466e8a19470256966c8b,
title = "Transient endoreplication down-regulates the kinesin-14 HSET and contributes to genomic instability",
abstract = "Polyploid cancer cells exhibit chromosomal instability (CIN), which is associated with tumorigenesis and therapy resistance. The mechanisms that induce polyploidy and how these mechanisms contribute to CIN are not fully understood. Here we evaluate CIN in human cells that become polyploid through an experimentally induced endoreplication cycle. When these induced endoreplicating cells (iECs) returned to mitosis, it resulted in aneuploidy in daughter cells. This aneuploidy resulted from multipolar divisions, chromosome missegregation, and failure in cytokinesis. The iECs went through several rounds of division, ultimately spawning proliferative cells of reduced ploidy. iECs have reduced levels of the kinesin-14 HSET, which likely accounts for the multipolar divisions, and overexpression of HSET reduced spindle multipolarity. However, HSET overexpression had only mild effects on CIN, suggesting that additional defects must contribute to genomic instability in dividing iECs. Overall our results suggest that transient endoreplication cycles generate a diverse population of proliferative aneuploid cells that have the potential to contribute to tumor heterogeneity.",
author = "Shengyao Chen and Stout, {Jane R.} and Sathiya Dharmaiah and Sarah Yde and Calvi, {Brian R.} and Claire Walczak",
year = "2016",
month = "10",
day = "1",
doi = "10.1091/mbc.E16-03-0159",
language = "English (US)",
volume = "27",
pages = "2911--2923",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "19",

}

TY - JOUR

T1 - Transient endoreplication down-regulates the kinesin-14 HSET and contributes to genomic instability

AU - Chen, Shengyao

AU - Stout, Jane R.

AU - Dharmaiah, Sathiya

AU - Yde, Sarah

AU - Calvi, Brian R.

AU - Walczak, Claire

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Polyploid cancer cells exhibit chromosomal instability (CIN), which is associated with tumorigenesis and therapy resistance. The mechanisms that induce polyploidy and how these mechanisms contribute to CIN are not fully understood. Here we evaluate CIN in human cells that become polyploid through an experimentally induced endoreplication cycle. When these induced endoreplicating cells (iECs) returned to mitosis, it resulted in aneuploidy in daughter cells. This aneuploidy resulted from multipolar divisions, chromosome missegregation, and failure in cytokinesis. The iECs went through several rounds of division, ultimately spawning proliferative cells of reduced ploidy. iECs have reduced levels of the kinesin-14 HSET, which likely accounts for the multipolar divisions, and overexpression of HSET reduced spindle multipolarity. However, HSET overexpression had only mild effects on CIN, suggesting that additional defects must contribute to genomic instability in dividing iECs. Overall our results suggest that transient endoreplication cycles generate a diverse population of proliferative aneuploid cells that have the potential to contribute to tumor heterogeneity.

AB - Polyploid cancer cells exhibit chromosomal instability (CIN), which is associated with tumorigenesis and therapy resistance. The mechanisms that induce polyploidy and how these mechanisms contribute to CIN are not fully understood. Here we evaluate CIN in human cells that become polyploid through an experimentally induced endoreplication cycle. When these induced endoreplicating cells (iECs) returned to mitosis, it resulted in aneuploidy in daughter cells. This aneuploidy resulted from multipolar divisions, chromosome missegregation, and failure in cytokinesis. The iECs went through several rounds of division, ultimately spawning proliferative cells of reduced ploidy. iECs have reduced levels of the kinesin-14 HSET, which likely accounts for the multipolar divisions, and overexpression of HSET reduced spindle multipolarity. However, HSET overexpression had only mild effects on CIN, suggesting that additional defects must contribute to genomic instability in dividing iECs. Overall our results suggest that transient endoreplication cycles generate a diverse population of proliferative aneuploid cells that have the potential to contribute to tumor heterogeneity.

UR - http://www.scopus.com/inward/record.url?scp=84989883740&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989883740&partnerID=8YFLogxK

U2 - 10.1091/mbc.E16-03-0159

DO - 10.1091/mbc.E16-03-0159

M3 - Article

C2 - 27489338

AN - SCOPUS:84989883740

VL - 27

SP - 2911

EP - 2923

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 19

ER -