Figure 2

Following genotoxic insult (Mutations (for example: loss of tumor suppressor p53, cyclin-dependent kinase N2A (CDKN2A)); HPV infection, etc.) microenvironmental signals initiate and enhance pro-EMT pathology. Molecular signaling from the millieu promotes degradation of the extracellular matrix (ECM; Vimentin expression, matrix metalloproteinases (MMP) secretion); increased local and perineural invasion, angiogenesis, hyper mitotic features followed by hypoxia and intratumoral necrosis in parallel with tumor growth and metastasis.