The induction of endoreduplication and polyploidy by elevated expression of 14-3-3γ

Cecil J. Gomes, Sara M. Centuori, Michael W. Harman, Charles W. Putnam, Charles William Wolgemuth, Jesse D Martinez

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Several studies have demonstrated that specific 14-3-3 isoforms are frequently elevated in cancer and that these proteins play a role in human tumorigenesis. 14-3- 3γ, an isoform recently demonstrated to function as an oncoprotein, is overexpressed in a variety of human cancers; however, its role in promoting tumorigenesis remains unclear. We previously reported that overexpression of 14-3-3γ caused the appearance of polyploid cells, a phenotype demonstrated to have profound tumor promoting properties. Here we examined the mechanism driving 14-3-3γ-induced polyploidization and the effect this has on genomic stability. Using FUCCI probes we showed that these polyploid cells appeared when diploid cells failed to enter mitosis and subsequently underwent endoreduplication. We then demonstrated that 14-3-3γ-induced polyploid cells experience significant chromosomal segregation errors during mitosis and observed that some of these cells stably propagate as tetraploids when isolated cells were expanded into stable cultures. These data lead us to conclude that overexpression of the 14-3-3γ promotes endoreduplication. We further investigated the role of 14-3-3γ in human NSCLC samples and found that its expression is significantly elevated in polyploid tumors. Collectively, these results suggests that 14-3-3γ may promote tumorigenesis through the production of a genetically unstable polyploid intermediate.

Original languageEnglish (US)
Pages (from-to)771-783
Number of pages13
JournalGenes and Cancer
Volume8
Issue number11-12
DOIs
StatePublished - Nov 1 2017

Fingerprint

Endoreduplication
Polyploidy
Carcinogenesis
Mitosis
Neoplasms
Protein Isoforms
Tetraploidy
Genomic Instability
Oncogene Proteins
Diploidy
Phenotype
Proteins

Keywords

  • 14-3-3 gamma
  • Aneuploidy
  • Chromosomal instability
  • Non-small cell lung cancer
  • Polyploidy

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

The induction of endoreduplication and polyploidy by elevated expression of 14-3-3γ. / Gomes, Cecil J.; Centuori, Sara M.; Harman, Michael W.; Putnam, Charles W.; Wolgemuth, Charles William; Martinez, Jesse D.

In: Genes and Cancer, Vol. 8, No. 11-12, 01.11.2017, p. 771-783.

Research output: Contribution to journalArticle

Gomes, Cecil J. ; Centuori, Sara M. ; Harman, Michael W. ; Putnam, Charles W. ; Wolgemuth, Charles William ; Martinez, Jesse D. / The induction of endoreduplication and polyploidy by elevated expression of 14-3-3γ. In: Genes and Cancer. 2017 ; Vol. 8, No. 11-12. pp. 771-783.
@article{db1b635818604b5e886cd4713a9d9242,
title = "The induction of endoreduplication and polyploidy by elevated expression of 14-3-3γ",
abstract = "Several studies have demonstrated that specific 14-3-3 isoforms are frequently elevated in cancer and that these proteins play a role in human tumorigenesis. 14-3- 3γ, an isoform recently demonstrated to function as an oncoprotein, is overexpressed in a variety of human cancers; however, its role in promoting tumorigenesis remains unclear. We previously reported that overexpression of 14-3-3γ caused the appearance of polyploid cells, a phenotype demonstrated to have profound tumor promoting properties. Here we examined the mechanism driving 14-3-3γ-induced polyploidization and the effect this has on genomic stability. Using FUCCI probes we showed that these polyploid cells appeared when diploid cells failed to enter mitosis and subsequently underwent endoreduplication. We then demonstrated that 14-3-3γ-induced polyploid cells experience significant chromosomal segregation errors during mitosis and observed that some of these cells stably propagate as tetraploids when isolated cells were expanded into stable cultures. These data lead us to conclude that overexpression of the 14-3-3γ promotes endoreduplication. We further investigated the role of 14-3-3γ in human NSCLC samples and found that its expression is significantly elevated in polyploid tumors. Collectively, these results suggests that 14-3-3γ may promote tumorigenesis through the production of a genetically unstable polyploid intermediate.",
keywords = "14-3-3 gamma, Aneuploidy, Chromosomal instability, Non-small cell lung cancer, Polyploidy",
author = "Gomes, {Cecil J.} and Centuori, {Sara M.} and Harman, {Michael W.} and Putnam, {Charles W.} and Wolgemuth, {Charles William} and Martinez, {Jesse D}",
year = "2017",
month = "11",
day = "1",
doi = "10.18632/genesandcancer.161",
language = "English (US)",
volume = "8",
pages = "771--783",
journal = "Genes and Cancer",
issn = "1947-6019",
publisher = "SAGE Publications Inc.",
number = "11-12",

}

TY - JOUR

T1 - The induction of endoreduplication and polyploidy by elevated expression of 14-3-3γ

AU - Gomes, Cecil J.

AU - Centuori, Sara M.

AU - Harman, Michael W.

AU - Putnam, Charles W.

AU - Wolgemuth, Charles William

AU - Martinez, Jesse D

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Several studies have demonstrated that specific 14-3-3 isoforms are frequently elevated in cancer and that these proteins play a role in human tumorigenesis. 14-3- 3γ, an isoform recently demonstrated to function as an oncoprotein, is overexpressed in a variety of human cancers; however, its role in promoting tumorigenesis remains unclear. We previously reported that overexpression of 14-3-3γ caused the appearance of polyploid cells, a phenotype demonstrated to have profound tumor promoting properties. Here we examined the mechanism driving 14-3-3γ-induced polyploidization and the effect this has on genomic stability. Using FUCCI probes we showed that these polyploid cells appeared when diploid cells failed to enter mitosis and subsequently underwent endoreduplication. We then demonstrated that 14-3-3γ-induced polyploid cells experience significant chromosomal segregation errors during mitosis and observed that some of these cells stably propagate as tetraploids when isolated cells were expanded into stable cultures. These data lead us to conclude that overexpression of the 14-3-3γ promotes endoreduplication. We further investigated the role of 14-3-3γ in human NSCLC samples and found that its expression is significantly elevated in polyploid tumors. Collectively, these results suggests that 14-3-3γ may promote tumorigenesis through the production of a genetically unstable polyploid intermediate.

AB - Several studies have demonstrated that specific 14-3-3 isoforms are frequently elevated in cancer and that these proteins play a role in human tumorigenesis. 14-3- 3γ, an isoform recently demonstrated to function as an oncoprotein, is overexpressed in a variety of human cancers; however, its role in promoting tumorigenesis remains unclear. We previously reported that overexpression of 14-3-3γ caused the appearance of polyploid cells, a phenotype demonstrated to have profound tumor promoting properties. Here we examined the mechanism driving 14-3-3γ-induced polyploidization and the effect this has on genomic stability. Using FUCCI probes we showed that these polyploid cells appeared when diploid cells failed to enter mitosis and subsequently underwent endoreduplication. We then demonstrated that 14-3-3γ-induced polyploid cells experience significant chromosomal segregation errors during mitosis and observed that some of these cells stably propagate as tetraploids when isolated cells were expanded into stable cultures. These data lead us to conclude that overexpression of the 14-3-3γ promotes endoreduplication. We further investigated the role of 14-3-3γ in human NSCLC samples and found that its expression is significantly elevated in polyploid tumors. Collectively, these results suggests that 14-3-3γ may promote tumorigenesis through the production of a genetically unstable polyploid intermediate.

KW - 14-3-3 gamma

KW - Aneuploidy

KW - Chromosomal instability

KW - Non-small cell lung cancer

KW - Polyploidy

UR - http://www.scopus.com/inward/record.url?scp=85042936253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042936253&partnerID=8YFLogxK

U2 - 10.18632/genesandcancer.161

DO - 10.18632/genesandcancer.161

M3 - Article

VL - 8

SP - 771

EP - 783

JO - Genes and Cancer

JF - Genes and Cancer

SN - 1947-6019

IS - 11-12

ER -