Fig. 3

At the base of CSCs production, the EMT mechanism is involved and is associated with a decrease in mitochondrial activity and an increase in glycolysis. Signaling pathways implicated in EMT, such as Wnt/β-catenin, are also involved in the stimulation of stemness characteristics and the acquisition of CSCs. Regulation of metabolic adaptation can occur with the help of molecules involved in EMT such as Wnt and AKT, STAT3, Snail, HIF-1α, TGF-β, and Dlx-2. Cancer-associated fibroblasts (CAFs) induce tumor remodeling through the release of factors such as matrix metalloproteinases (MMPs) and enzymes, and angiogenesis that summons other inhibitory cells, growth, and metastasis. Lactate released by CAFs following glycolytic metabolism in these cells is taken up and used by CSCs such as epithelial cells to supply the TCA cycle, which in turn promotes processes such as metastasis, self-renewal, and invasion of MSCs provide