Table 2.

ARF6 signaling pathways in development and disease.

Biologic Process	Signaling Pathway	Outcome/Model System	References
Development	Schizo/Loner-Arf6	neural commissure formation, Drosophila	Onel et al.19
	Schizo/Loner-Arf6	myoblast fusion, Drosophila	Chen et al.20
	ARF6	early embryo formation, sea urchin	Dumas et al.21
	HGF-ARF6	liver development, mice	Suzuki et al.17
Barrier Structure & Function
Endothelial	IL1R-MYD88-ARNO-ARF6	collagen-induced arthritis, mice	Zhu et al.18
	VEGF-ARNO-ARF6-RAC1 inhibited by SLIT2/ROBO4-GIT1-Paxillin	1. retinal permeability, retinopathy, mice 2. retinal neovascularization, macular degeneration, mice	Jones et al.26
	LPS-TLR4-MYD88-ARNO-ARF6-VEcadherin	endotoxic shock/sepsis, mice	Davis et al.25
	HGF-ARF6 GEFs*-β1integrin	tumor neoangiogenesis, mice	Hongu et al.22
Epithelial	HGF-ARF6-Ecadherin	epithelial cell migration, in vitro	Palacios et al.35,36
	HGF-ARF6-RAC1	epithelial tube formation**, in vitro	Tushir and D'Souza-Schorey54
	WNT3A-ARF6-cMET-ERK-CK2-Ecadherin/βcatenin	abnormal cyst filling/ductular proliferation, in vitro	Pellon-Cardenas et al.27
Cancer
glioma	HGF-ARF6-IQGAP1-RAC1	invasion in vitro, invasion in mice	Hu et al.49
cutaneous melanoma	HGF-ARF6-ERK	invasion, in vitro	Tague et al.52
cutaneous melanoma	WNT5A/FZD4/LRP6-GEP100-ARF6-βcatenin	invasion in vitro, spontaneous lung metastasis in mice	Grossmann et al.13
breast carcinoma	EGFR-GEP100-ARF6-AMAP1	invasion in vitro, experimental metastasis+ in mice	Morishige et al.51, Onodera et al.61
lung adenocarcinoma	HER2-GEP100-ARF6-AMAP1	invasion, in vitro	Menju et al.50
renal cell carcinoma	LPAR2-Gα12-EFA6-ARF6	invasion in vitro, experimental metastasis2+ in mice	Hashimoto et al.63
uveal melanoma	GNAQQ209L-GEP100-ARF6-PLC, ERK, YAP and βcatenin	proliferation and colony formation in vitro, tumor establishment and growth in mice	Yoo et al.16

ARF6 mediates a variety of biologic processes. In developing organisms, ARF6 is essential for embryogenesis. In mature organisms, ARF6 activation potentiates both inflammatory and neoplastic disease states. *Multiple ARF6 GEFs were implicated. **Also relevant to development of 3-dimensional epithelial structures in various organs. +Tail vein injection model. ++Tail vein injection model with bioluminescent scoring, no gross or microscopic lung masses reported.