Recombinant viral capsid protein VP1 suppresses migration and invasion of human cervical cancer by modulating phosphorylated prohibitin in lipid rafts
Recombinant viral capsid protein VP1 suppresses migration and invasion of human cervical cancer by modulating phosphorylated prohibitin in lipid rafts
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DOI：
10.1016/j.canlet.2012.02.027
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发表时间：
2012-07-28
期刊：
影响因子：
9.7
通讯作者：
Liang, Shu-Mei
中科院分区：
文献类型：
--
作者：
Chiu, Ching-Feng;Peng, Jei-Ming;Liang, Shu-Mei
口蹄疫病毒重组衣壳蛋白VP1（rVP1）抑制癌细胞的侵袭/转移。在这里我们研究了它对人宫颈癌细胞的作用机制。 rVP1 对细胞侵袭的抑制伴随着脂筏中磷脂酰肌醇 (3,4,5)-三磷酸 (PIP3)、磷酸化 Akt 5473、磷酸化抑制素 (磷酸化 PHB) T258 的减少、磷酸化 PHB 1258 与 Raf-1 的解离以及 Raf-1/ERK 的失活。添加 PIP3 或过表达组成型活性 Akt 和筏锚定的 PHB 1258（而非 PHB 12581 突变蛋白）可逆转 rVP1 的抑制作用。 rVP1 抑制宫颈肿瘤的生长和转移，并延长异种移植小鼠模型的生存期。这些结果表明，rVP1 通过脂筏中 Akt 和 PHB T258 的去磷酸化下调 Raf/ERK 信号传导来抑制癌症转移。 (C) 2012 Elsevier Ireland Ltd. 保留所有权利。
Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus inhibits invasion/metastasis of cancer cells. Here we studied its mechanism of action on human cervical cancer cells. The inhibition of cell invasion by rVP1 was accompanied with reduction in phosphatidylinositol (3,4,5)-triphosphate (PIP3), phospho-Akt 5473, phosphorylated prohibitin (phospho-PHB) T258 in lipid rafts, dissociation of phospho-PHB 1258 with Raf-1 and the inactivation of Raf-1/ERK. Addition of PIP3 or overexpression of constitutively active Akt and raft-anchored PHB 1258 but not PHB 12581 mutant protein reversed the inhibitory effects of rVP1. rVP1 inhibited cervical tumor growth and metastasis, and prolonged survival in xenograft mouse models. These results suggest that rVP1 inhibits cancer metastasis via de-phosphorylation of Akt and PHB T258 in lipid rafts to downregulate Raf/ERK signaling. (C) 2012 Elsevier Ireland Ltd. All rights reserved.