GSE119449
Septin 9 over expression in MCF7
Septin 9 (SEPT9), a member of the septin gene family, is strongly linked to cancer, particularly breast cancer, where genomic amplification occurs in ~11% of cases. SEPT9 is a putative oncogene as it is amplified in the form of double minute chromosomes in murine models of breast cancer, is a fusion partner of mixed lineage leukemia (MLL) gene in leukemia, and it is a known hot spot of retroviral tagging insertion. SEPT9 contributes to cytoskeleton dynamics, thus oncogenic functions have been proposed based on the broad range of cellular functions it partakes. Yet, a clear mechanism by which SEPT9 elicits tumor-promoting functions is lacking. To obtain unbiased insights on molecular signatures of SEPT9 upregulation in breast tumors, we overexpressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supports a role of SEPT9 in invasion. Functional studies indicate that SEPT9 upregulation is sufficient to increase degradation of the extracellular matrix, while its downregulation inhibits this process. The degradation pattern is associated with focal adhesions (FA) at the cell periphery. Increased extracellular matrix digestion during epithelial–mesenchymal transition digestion is significantly associated with increased expression of matrix metalloproteinases. In SEPT9 over expressing cells, MMP3 is secreted to the media at FAs. Downregulation of SEPT9 or chemical inhibition of septin filaments assembly impairs recruitment of MMP3 to FAs. Our results indicate that SEPT9 promotes both trafficking and secretion of MMPs near FAs, thus enhancing migration and invasion of breast cancer cells. Overall design: MCF7_SEPT9_v1, MCF7_SEPT9_v2, and MCF7_SEPT9_v3-overexpressing cell lines and the MCF7 control cells (MCF7_C) were used. A total of 12 samples were used for RNA-Seq analysis (three biological replicates from each of the MCF-7 isoforms and control cells).