Slingshot-1L, a cofilin phosphatase, induces primary breast cancer metastasis.
Slingshot-1L, a cofilin phosphatase, induces primary breast cancer metastasis.
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DOI：
10.18632/oncotarget.19855
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Tao H
中科院分区：
文献类型：
--
作者：
Chen C;Maimaiti Y;Zhijun S;Zeming L;Yawen G;Pan Y;Tao H
弹弓（Slingshot，SSH）是保守的cofilin磷酸酶家族的成员，通过将失活的磷酸化cofilin转化为活性形式，在细胞膜突起和迁移中起关键作用。SSH样蛋白1（SSH-1 L）的表达在各种类型的肿瘤中检测到;胰岛素诱导磷酸肌醇3-激酶依赖性的磷酸酶活性的SSH-1 L。然而，关于SSH-1 L在乳腺癌中的表达和作用知之甚少。在这里，我们分析了295人乳腺癌组织标本的SSH-1 L表达的免疫组化。采用Pearson's χ2检验分析SSH-1 L水平与患者临床特征的相关性。通过基因敲低和实时定量聚合酶链反应检测MDA-MB-231、MCF-7和SK-BR-3人乳腺癌细胞系中cofilin的表达来评估SSH-1 L的功能。SSH-1 L的表达检测到88.1%的组织标本的免疫组化和强烈相关的转移和死亡率增加。在SK-BR-3和MDA-MB-231细胞系中，SSH-1 L表达的缺失降低了非磷酸化的、活性形式的cofilin，这与细胞运动性降低有关。因此，SSH-1 L/cofilin信号通路在乳腺癌转移中起着重要作用，是乳腺癌治疗的潜在靶点。
Slingshot (SSH) is a member of the conserved family of cofilin phosphatases that plays a critical role in cell membrane protrusion and migration by transforming inactive phosphorylated cofilin to an active form. SSH-like protein 1 (SSH-1L) expression is detected in various types of tumors; insulin induces the phosphatases activity of SSH-1L in a phosphoinositide 3-kinase-dependent manner. However, little is known about the expression and role of SSH-1L in breast cancer. Here, we analyzed 295 human breast cancer tissue specimens for SSH-1L expression by immunohistochemistry. The correlation between SSH-1L level and patients’ clinical characteristics was analyzed with Pearson’s χ2 test. The function of SSH-1L was evaluated by gene knockdown and quantitative real-time polymerase chain reaction detection of cofilin expression in MDA-MB-231, MCF-7, and SK-BR-3 human breast cancer cell lines. SSH-1L expression was detected in 88.1% of tissue specimens by immunohistochemistry and was strongly associated with increased metastasis and mortality. Loss of SSH-1L expression decreased the nonphosphorylated, active form of cofilin in SK-BR-3 and MDA-MB-231 cell lines, which was associated with reduced cell motility. Accordingly, SSH-1L/cofilin signaling played a critical role in primary breast cancer metastasis and was a potential therapeutic target for breast cancer treatment.
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