Seeing that ARNO is the only Arf6-specific GEF highly expressed in liver cancer tissues (Figs. 6, 7), it is most probably that HGF activates Arf6 by recruiting ARNO to the endomembrane (including endosomes), which subsequently triggers the activation of Rac1 and other downstream effectors (e.g. phospholipase D) through an as yet unknown mechanism. The gene discussed is HGF; the disease is liver cancer.