If the production of these ligands is upregulated in obesity, there are significant implications for EGFR-mediated cell proliferation, invasion, and metastasis of epithelial malignancies via downstream activation of the ERK, PI3 kinase/AKT, and JAK/STAT pathways [32, 33]. This evidence concerns the gene AKT1 and obesity due to melanocortin 4 receptor deficiency.