Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments

Autor: Verdier-Pinard, P., Salaun, D., Bouguenina, H., Shimada, S., Pophillat, M., Audebert, S., Agavnian, E., Coslet, S., Charafe-Jauffret, E., Tachibana, T., Badache, A.
Přispěvatelé: Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Science et Ingénierie des Matériaux et Procédés (SIMaP ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), EDF (EDF), Kyoto University [Kyoto], Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Science et Ingénierie des Matériaux et Procédés [2007-2015] (SIMaP [2007-2015]), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), MITOYAN, Louciné, Kyoto University
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Scientific Reports
Scientific Reports, Nature Publishing Group, 2017, 7, ⟨10.1038/srep44976⟩
Scientific Reports, 2017, 7, ⟨10.1038/srep44976⟩
ISSN: 2045-2322
DOI: 10.1038/srep44976⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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