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NNMT alters Akt phosphorylation and affects the association between the transcription factor SP1 and the MMP2 promoter ( NNMT knockdown in a more aggressive squamous cell line contributed to the downregulation of epithelial–mesenchymal transition (EMT)-related genes, including MMP9 , osteopontin ( OPN ), and versican core protein ( VCAN ), which are involved in focal adhesion and extracellular matrix (ECM)–receptor interaction ( Cancer-associated fibroblasts (CAFs) are a fibroblast subpopulation that secrete pro-oncogenic cytokines and ECM-modifying factors promoting and supporting malignant cell growth and invasion (75)