MMP9 and neoplasm: Additionally, given that the metastatic spread of tumor cells is a multi-stage process involving a series of complex physiological events, MMP-2 and MMP-9 expression is regulated by a complicated network of signaling pathways that can be activated by a range of growth factors, cytokines, and chemicals such as PI3K/Akt, p38-MAPK, NF-κB, EGFR, ERK1/2, and TPA, acting via a number of pathways, such as the MAPK/ERK pathway [39–45].