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Cancer Res：卵巢癌中CIB2通过神经鞘氨醇激酶1负调控致癌信号通路

2017-07-24 MedSci MedSci原创

卵巢癌SK1信号通路抑制因子
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鞘氨醇激酶1(SK1)是促凋亡和促生存神经脂质中关键的细胞平衡调节器。受SK1调控的致癌信号通路需要依赖SK1定位到质膜上，其定位通过Ca2+十四酰开关功能被钙离子和整合素结合蛋白CIB1介导。本文中，我们研究了CIB家族中的另一个成员CIB2，CIB2在SK1信号通路的调控中发挥着与CIB1截然相反的作用。CIB2能够和SK1结合，结合位点与CIB1相同，但是CIB2缺乏Ca2+十四酰开关功能。

鞘氨醇激酶1(SK1)是促凋亡和促生存神经脂质中关键的细胞平衡调节器。

受SK1调控的致癌信号通路需要依赖SK1定位到质膜上，其定位通过Ca2+十四酰开关功能被钙离子和整合素结合蛋白CIB1介导。

本文中，我们研究了CIB家族中的另一个成员CIB2，CIB2在SK1信号通路的调控中发挥着与CIB1截然相反的作用。CIB2能够和SK1结合，结合位点与CIB1相同，但是CIB2缺乏Ca2+十四酰开关功能。因此，CIB2阻断了SK1在质膜上的定位，从而阻止了后续信号传递，包括对TNFα诱导的细胞凋亡的敏化作用以及Ras诱导的肿瘤转变。

卵巢癌中CIB2显著下调，低表达的CIB2与卵巢癌患者的不良预后相关。值得注意的是卵巢癌细胞中再次引入CIB2会阻断内源SK1定位到质膜上，降低体外肿瘤增长，并且抑制体内体外细胞的运动性和侵袭性，这些与SK1特异性抑制剂SK1-I 和标准化疗两者间的体外协同效果一致。同时，表达CIB2会使卵巢癌细胞对顺羧酸铂敏感。

综合而言，这些发现表明CIB2是一种新型的内源性SK1信号通路抑制子，可以作为一种潜在的预后标记，表征在妇科恶性肿瘤治疗中的效果。


原文出处：Zhu, W., et al., CIB2 negatively regulates oncogenic signaling in ovarian cancer via sphingosine kinase 1. Cancer Res, 2017 Jul 20 doi: 10.1158/0008-5472.CAN-17-0025.

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    2017-07-26 智者为医08

    #信号通路#

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