Table 1. ^* qRT-PCR - Human Melanoma Cells + CVM-1118.

Decrease in mRNA
↓Decrease	Notes
Nodal	TGF-β family member, binds to ALK4/5/7 and ActRllB/TGF-β- R2 activin-like kinase receptors to signal through SMAD2/3. Blocking Nodal signaling blocks VM. (Hardy et al., 2010; Kirschmann et al. 2012)
pSMAD2	Published that decrease in Nodal results in a decrease in p- SMAD2 signaling and decrease in VM. (Hardy et al., 2010)
Notch4 ICD	Published that knock-down Notch4 results in decrease in Nodal expression and decrease in VM. Notch binding to its receptor results in cleavage of Notch, releasing an Intracellular domain (NICD) which translocates into the nucleus and regulates the expression of a number of targets, including Nodal (Hardy et al., 2010; Kirschmann et al., 2012). Notch is downstream of VEGF signaling (Takeshita et al., 2007). Notch1 activates p21-induced cell-cycle arrest tumor model (Liu et al., 2015). Increase in Notch has been associated with a decrease in p27 (Sharma et al., 2010). p53 regulates Notch activation (Laws and Osborne, 2004). Notch is a p53 target with a role in human tumor suppression (Lefort et al., 2007).
HES1	A target protein of Notch (Sharma et al., 2010) and plays a role in cellular differentiation, cell cycle arrest, apoptosis and self-renewal, maintaining cancer stem cells (CSC), metastasis and antagonizing drug-induced apoptosis (Liu et al., 2015). HES1 transcriptionally represses p21 (Liu et al., 2015)).
VEGF-A	VEGF treatment of cells results in Notch1 cleavage and increase in HES1 expression (Takeshita et al., 2007). WT p53 represses VEGF expression (Ghahremani et al., 2013).

^*qRT-PCR performed in triplicate with primers previously published (Hardy et al., 2010), and key data further validated by Western blot analyses.