These authors contributed equally to the article.
SEPT9_i1 and genomic instability: Mechanistic insights and relevance to tumorigenesis
Article first published online: 24 AUG 2011
Copyright © 2011 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 50, Issue 11, pages 940–949, November 2011
How to Cite
Peterson, E. A., Stanbery, L., Li, C., Kocak, H., Makarova, O. and Petty, E. M. (2011), SEPT9_i1 and genomic instability: Mechanistic insights and relevance to tumorigenesis. Genes Chromosom. Cancer, 50: 940–949. doi: 10.1002/gcc.20916
- Issue published online: 11 SEP 2011
- Article first published online: 24 AUG 2011
- Manuscript Accepted: 12 JUL 2011
- Manuscript Received: 28 FEB 2011
- NIH National Research Service Award. Grant Number: 5-T32-GM07544
- NRSA Predoctoral Individual Fellowship to Promote Diversity in Health-Related Research. Grant Number: 1F31CA123639-01-A1
- Department of Defense Breast Cancer Research Program Post-Doctoral Grant. Grant Number: W81XWH-10-1-0545
- NIH National Cancer Institute Grant. Grant Number: RO1CA072877
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. © 2011 Wiley-Liss, Inc.