Debinski and Gibo (2005) hypothesized that any AP1-stimulating signals like epidermal growth factor (EGF), leukemia inhibitory factor, OSMR, or FGF-2 can positively regulate FRA-1. VEGF-D is regulated by FRA-1 (supporting the feedback loop found in our work) and is a known prognostic factor in other aggressive cancers (Debinski et al., 2001; Azar et al., 2014). This evidence concerns the gene VEGFD and cancer.