Importantly, CAFs also play an important role in modulating the microenvironment by remodulating and degrading the TME and contribute to epithelial to mesenchymal transition (EMT) via the transglutaminase 2-dependent IL-6/IL6R/STAT3 axis, matrix-metalloproteinase (MMP) production, i.e., MMP-2, MMP-3; they also increase vimentin expression and downregulate the adhesion molecules e-cadherin, desmoglein 1 and 3, desmoplakin and desmocollin, which results in the promotion of the invasive phenotype of cancer cells in HNSCC. Here, STAT3 is linked to cancer.