FIGURE 11: Graphical Summary. In the TME, the interaction between fibroblasts and carcinoma cells stimulates oxidative stress with reactive oxygen species (ROS) release. ROS in fibroblasts triggers DNA hypomethylation leading to miR-200c transcriptional enrichment. MET in fibroblasts via miR-200c induces senescence, miR-205 and suppresses COMMD1 that activates NFκB and HIF signaling and recapitulates the phenotype of CAFs with downregulation of CAV1 and upregulation of MCT4 as well as cytokines, growth factors and lactate release. Paramountly, these reprogrammed fibroblasts promote cancer aggressiveness.