title: Pathological functions of the small GTPase Arf6 in cancer progression: Tumor angiogenesis and metastasis.
abstract: 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.
authors.affiliation: a Department of Physiological Chemistry , Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba , Japan.
authors.forename: Tsunaki
authors.initials: T
authors.lastname: Hongu
authors.affiliation: a Department of Physiological Chemistry , Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba , Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamauchi
authors.affiliation: a Department of Physiological Chemistry , Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba , Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Funakoshi
authors.affiliation: a Department of Physiological Chemistry , Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba , Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Katagiri
authors.affiliation: a Department of Physiological Chemistry , Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba , Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ohbayashi
authors.affiliation: a Department of Physiological Chemistry , Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba , Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kanaho
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D018450:Disease Progression; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology*; D009389:Neovascularization, Pathologic
chemical_list: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse
keywords: Arf6; HGF; cancer cell invasion; cancer metastasis; tumor angiogenesis; tumor growth; β1 integrin recycling