SEPT9-i1 and genomic instability: Mechanistic insights and relevance to tumorigenesis

Esther A. Peterson, Laura Stanbery, Christina Li, Hande Kocak, Olga Makarova, Elizabeth M. Petty

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Septins are highly conserved cytoskeletal GTP-binding proteins implicated in numerous cellular processes from apoptosis to vesicle trafficking. Septins have been associated with leukemia and solid tumor malignancies, including breast, ovarian, and prostate. We previously reported that high SEPT9-i1 expression in human mammary epithelial cell lines (HMECs) led to malignant cellular phenotypes such as increased cell proliferation, invasiveness, motility, and genomic instability. Our goal here was to better understand how SEPT9-i1 expression might contribute to genomic instability and malignant progression. First, we confirmed that even transient expression of SEPT9-i1 was sufficient to increase aneuploidy in HMECs. We then analyzed SEPT9-i1 by immunoprecipitation and immunofluorescence studies and found that SEPT9-i1 interacts with both α and γ tubulin. SEPT9-i1 expressing cells demonstrated dramatic chromosome segregation defects, centrosome amplification and cytokinesis defects, suggesting two possible molecular mechanisms contributing to the development of genomic instability. This suggests that SEPT9-i1 may promote genomic instability through both cytokinesis and mitotic spindle defects which lead to chromosome missegregation.

Original languageEnglish (US)
Pages (from-to)940-949
Number of pages10
JournalGenes Chromosomes and Cancer
Volume50
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

Genomic Instability
Carcinogenesis
Septins
Breast
Cytokinesis
Epithelial Cells
Cell Line
Centrosome
Chromosome Segregation
Spindle Apparatus
Cytoskeletal Proteins
Aneuploidy
Tubulin
GTP-Binding Proteins
Immunoprecipitation
Fluorescent Antibody Technique
Prostate
Neoplasms
Leukemia
Chromosomes

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Peterson, E. A., Stanbery, L., Li, C., Kocak, H., Makarova, O., & Petty, E. M. (2011). SEPT9-i1 and genomic instability: Mechanistic insights and relevance to tumorigenesis. Genes Chromosomes and Cancer, 50(11), 940-949. https://doi.org/10.1002/gcc.20916

SEPT9-i1 and genomic instability : Mechanistic insights and relevance to tumorigenesis. / Peterson, Esther A.; Stanbery, Laura; Li, Christina; Kocak, Hande; Makarova, Olga; Petty, Elizabeth M.

In: Genes Chromosomes and Cancer, Vol. 50, No. 11, 11.2011, p. 940-949.

Research output: Contribution to journalArticle

Peterson, EA, Stanbery, L, Li, C, Kocak, H, Makarova, O & Petty, EM 2011, 'SEPT9-i1 and genomic instability: Mechanistic insights and relevance to tumorigenesis', Genes Chromosomes and Cancer, vol. 50, no. 11, pp. 940-949. https://doi.org/10.1002/gcc.20916
Peterson, Esther A. ; Stanbery, Laura ; Li, Christina ; Kocak, Hande ; Makarova, Olga ; Petty, Elizabeth M. / SEPT9-i1 and genomic instability : Mechanistic insights and relevance to tumorigenesis. In: Genes Chromosomes and Cancer. 2011 ; Vol. 50, No. 11. pp. 940-949.
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