Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments.
Functions of septin cytoskeletal polymers in tumorigenesis are still poorly defined. Their role in the regulation of cytokinesis and cell migration were proposed to contribute to cancer associated aneuploidy and metastasis. Overexpression of Septin 9 (Sept9) promotes migration of cancer cell lines. SEPT9 mRNA and protein expression is increased in breast tumors compared to normal and peritumoral tissues and amplification of SEPT9 gene was positively correlated with breast tumor progression. However, the existence of multiple isoforms of Sept9 is a confounding factor in the analysis of Sept9 functions. In the present study, we analyze the protein expression of Sept9_i2, an uncharacterized isoform, in breast cancer cell lines and tumors and describe its specific impact on cancer cell migration and Sept9 cytoskeletal distribution. Collectively, our results showed that, contrary to Sept9_i1, Sept9_i2 did not support cancer cell migration, and induced a loss of subnuclear actin filaments. These effects were dependent on Sept9_i2 specific N-terminal sequence. Sept9_i2 was strongly down-regulated in breast tumors compared to normal mammary tissues. Thus our data indicate that Sept9_i2 is a negative regulator of breast tumorigenesis. We propose that Sept9 tumorigenic properties depend on the balance between Sept9_i1 and Sept9_i2 expression levels.
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Verdier-Pinard
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Salaun
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Bouguenina
Department of Bioengineering, Graduate School of Engineering, Osaka City University, Osaka, Japan.
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Shimada
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Pophillat
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Audebert
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Agavnian
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Coslet
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Charafe-Jauffret
Department of Bioengineering, Graduate School of Engineering, Osaka City University, Osaka, Japan.
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Tachibana
Centre de Recherche en Cancérologie de Marseille, INSERM, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Marseille, France.
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Badache
D008841:Actin Cytoskeleton / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005091:Exons; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms; D058112:Septins / Q000235:genetics* / Q000378:metabolism*
D020033:Protein Isoforms; C474315:SEPTIN9 protein, human; D058112:Septins