MAPK3 and neoplasm: A recently discovered key process in HNC cancerogenesis is the positive feedback loop between GDF15 and the early growth response 1 (EGR1) gene; GDF15 promotes tumor progression by directly activating EGR1 and performing a paracrine regulation of its expression through phosphorylation of ERK1/2 and AKT; conversely, EGR1 actively binds the GDF15 gene promoter, resulting in GDF15 overexpression.