Visfatin derived from ascites promotes ovarian cancer cell migration through Rho/ROCK signaling-mediated actin polymerization
Visfatin derived from ascites promotes ovarian cancer cell migration through Rho/ROCK signaling-mediated actin polymerization
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DOI：
10.1097/cej.0000000000000064
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发表时间：
2015-05-01
影响因子：
2.4
通讯作者：
Zhu, Yu
中科院分区：
文献类型：
--
作者：
Li, Yan;Li, Xun;Zhu, Yu
卵巢癌的特点是腹膜内扩散迅速，伴有腹水积聚。然而，卵巢癌腹膜内传播的确切机制仍不清楚。内脂素是一种新的脂肪因子，在多种肿瘤中血清内脂素水平升高。在此，我们发现腹水中内脂素水平升高与卵巢癌腹腔内转移有关。通过transwell细胞迁移实验和创伤愈合实验，我们发现腹水来源的内脂素可以促进Caov-3细胞的迁移。内脂素可诱导Caov-3细胞内肌动蛋白应力纤维聚集，形成板状伪足和丝状伪足，并使G-actin向F-actin转变。用细胞松弛素D抑制肌动蛋白聚合，可明显消除内脂素对Caov-3细胞迁移的影响。进一步的结果表明，内脂素以时间依赖性方式触发Rho激活及其下游cofilin磷酸化，从而导致肌动蛋白聚合。更重要的是，visfatin诱导的Caov-3细胞迁移被有效地阻断C3外切酶和Y27632，Rho，和ROCK抑制剂，分别。因此，我们的研究表明，腹水来源的内脂素促进卵巢癌细胞的迁移，通过Rho/ROCK信号介导的肌动蛋白聚合，这是卵巢癌腹膜内扩散所必需的。这些发现为卵巢癌腹膜内转移提供了一种新的分子机制，可能成为卵巢癌治疗的潜在靶点。版权所有（C）2015威科医疗集团All rights reserved.
Ovarian cancer is characterized by a rapid intraperitoneal spread combination with ascites accumulation. However, the exact mechanisms for ovarian cancer intraperitoneal dissemination remain unknown. Visfatin has recently been established as a novel adipokine and its serum level is increased in various cancers. Here, we identified that the elevated level of visfatin in ascites was associated with ovarian cancer intraperitoneal dissemination. Using the transwell cell migration assay and the wound-healing assay, we found that ascites-derived visfatin could promote migration of Caov-3 cells. Meanwhile, visfatin could induce the aggregation of actin stress fibers and the formation of lamellipodia and filopodia in Caov-3 cells, concomitant with a shift of G-actin to F-actin. Inhibition of actin polymerization with cytochalasin D obviously abolished the effects of visfatin on the migration of Caov-3 cells. Further results showed that visfatin triggered Rho activation and its downstream cofilin phosphorylation in a time-dependent manner, which led to actin polymerization. More importantly, visfatin-induced Caov-3 cell migration was effectively blocked by C3 exoenzyme and Y27632, Rho, and ROCK inhibitor, respectively. Thus, our study showed that ascites-derived visfatin promoted migration of ovarian cancer cells through Rho/ROCK signaling-mediated actin polymerization, which was required for ovarian cancer intraperitoneal dissemination. These findings offered a novel molecular mechanism responsible for ovarian cancer intraperitoneal dissemination, which might be a potential target for ovarian cancer management. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.