Yamauchi Yohei, Miura Yuki, Kanaho Yasunori
Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Adv Biol Regul. 2017 Jan;63:115-121. doi: 10.1016/j.jbior.2016.10.004. Epub 2016 Oct 18.
The Small GTPase ADP-ribosylation factor 6 (Arf6) functions as the molecular switch in cellular signaling pathways by cycling between GDP-bound inactive and GTP-bound active form, which is precisely regulated by two regulators, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Numerous studies have shown that these machineries play critical roles in tumor angiogenesis/growth and cancer cell invasion/metastasis through regulating the cycling of Arf6. Here, we summarize accumulating knowledge for involvement of Arf6 GEFs/GAPs and small molecule inhibitors of Arf6 signaling/cycling in cancer progression, and discuss possible strategies for developing innovative anti-cancer drugs targeting Arf6 signaling/cycling.
小GTP酶ADP核糖基化因子6（Arf6）作为细胞信号通路中的分子开关，通过在结合GDP的无活性形式和结合GTP的活性形式之间循环来发挥作用，这一过程由鸟嘌呤核苷酸交换因子（GEFs）和GTP酶激活蛋白（GAPs）这两种调节因子精确调控。大量研究表明，这些机制通过调节Arf6的循环，在肿瘤血管生成/生长以及癌细胞侵袭/转移中发挥关键作用。在此，我们总结了关于Arf6 GEFs/GAPs以及Arf6信号传导/循环的小分子抑制剂参与癌症进展的不断积累的知识，并讨论了开发靶向Arf6信号传导/循环的创新抗癌药物的可能策略。
