title: SEPT9_i1 and genomic instability: mechanistic insights and relevance to tumorigenesis.
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.
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Esther A
authors: EA
authors: Peterson
authors: Laura
authors: L
authors: Stanbery
authors: Christina
authors: C
authors: Li
authors: Hande
authors: H
authors: Kocak
authors: Olga
authors: O
authors: Makarova
authors: Elizabeth M
authors: EM
authors: Petty
mesh_terms: D000782:Aneuploidy; D015153:Blotting, Western; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D048749:Cytokinesis / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D042822:Genomic Instability; D045325:HCT116 Cells; D006801:Humans; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D008938:Mitosis; D058112:Septins / Q000235:genetics* / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics; D014162:Transfection; D014404:Tubulin / Q000378:metabolism
chemical_list: D014404:Tubulin; C474315:SEPTIN9 protein, human; D058112:Septins