Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments.
Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments.
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DOI：
10.1038/srep44976
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发表时间：
2017-03-24
影响因子：
4.6
通讯作者：
Badache A
中科院分区：
文献类型：
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作者：
Verdier-Pinard P;Salaun D;Bouguenina H;Shimada S;Pophillat M;Audebert S;Agavnian E;Coslet S;Charafe-Jauffret E;Tachibana T;Badache A
Septin细胞骨架聚合物在肿瘤发生中的作用尚不清楚。它们在胞质分裂和细胞迁移的调节中的作用被认为有助于癌症相关的非整倍体和转移。Septin 9(SEPT9)的过表达促进癌细胞的迁移。乳腺肿瘤组织中SEPT9基因的表达高于正常组织和癌旁组织，且SEPT9基因扩增与肿瘤进展呈正相关。然而，SEPT9多个亚型的存在是分析SEPT9功能的一个混杂因素。在本研究中，我们分析了一个未知的亚型SEPT9_i2在乳腺癌细胞系和肿瘤中的蛋白表达，并描述了它对癌细胞迁移和SEPT9细胞骨架分布的特殊影响。综上所述，我们的结果表明，与SEPT9_i1相反，SEPT9_i2不支持癌细胞迁移，并诱导亚核肌动蛋白细丝丢失。这些作用依赖于SEPT9_i2特异的N-末端序列。与正常乳腺组织相比，SEPT9_i2在乳腺肿瘤中的表达显著下调。因此，我们的数据表明SEPT9_i2是乳腺肿瘤发生的负调控因子。我们认为SEPT9的致瘤特性依赖于SEPT9_i1和SEPT9_i2表达水平之间的平衡。
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.