Pathological functions of the small GTPase Arf6 in cancer progression: Tumor angiogenesis and metastasis.
Pathological functions of the small GTPase Arf6 in cancer progression: Tumor angiogenesis and metastasis.
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小GTPase ARF6在癌症进展中的病理功能：肿瘤血管生成和转移。
DOI：
10.1080/21541248.2016.1154640
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发表时间：
2016-04-02
期刊：
影响因子：
--
通讯作者：
Kanaho Y
中科院分区：
文献类型：
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作者：
Hongu T;Yamauchi Y;Funakoshi Y;Katagiri N;Ohbayashi N;Kanaho Y
尽管多项证据表明小 GTP 酶 ADP 核糖基化因子 6 (Arf6) 在多种癌症的进展中发挥着关键作用，但人们对 Arf6 在肿瘤微环境中的功能知之甚少。我们通过植入 B16 黑色素瘤细胞和 Lewis 肺癌细胞的内皮细胞特异性 Arf6 条件敲除小鼠，证明了血管内皮细胞 (VEC) 中的 Arf6 在肿瘤血管生成和生长中发挥着至关重要的作用。还发现VEC中的Arf6正向调节肝细胞生长因子（HGF）诱导的β1整合素再循环，这是通过促进细胞迁移而导致肿瘤血管生成的关键事件。重要的是，药物抑制 HGF 诱导的 Arf6 激活可显着抑制小鼠肿瘤血管生成和生长，这表明 Arf6 信号传导将成为抗血管生成治疗的潜在靶点。在这篇手稿中，我们总结了 Arf6 在癌症进展中的多重作用，特别是在癌细胞侵袭/转移中以及我们最近在肿瘤血管生成方面的发现，并讨论了开发创新抗癌药物的可能方法。
Although several lines of evidence have shown that the small GTPase ADP-ribosylation factor 6 (Arf6) plays pivotal roles in cancer progression of several types of cancers, little is known about the functions of Arf6 in tumor microenvironment. We demonstrated that Arf6 in vascular endothelial cells (VECs) plays a crucial role in tumor angiogenesis and growth using endothelial cell-specific Arf6 conditional knockout mice into which B16 melanoma and Lewis lung carcinoma cells were implanted. It was also found that Arf6 in VECs positively regulates hepatocyte growth factor (HGF)-induced β1 integrin recycling, which is a critical event for tumor angiogenesis by promoting cell migration. Importantly, pharmacological inhibition of HGF-induced Arf6 activation significantly suppresses tumor angiogenesis and growth in mice, suggesting that Arf6 signaling would be a potential target for anti-angiogenic therapy. In this manuscript, we summarize the multiple roles of Arf6 in cancer progression, particularly in cancer cell invasion/metastasis and our recent findings on tumor angiogenesis, and discuss a possible approach to develop innovative anti-cancer drugs.