Metabolic reprogramming and plasticity of cancer stem cells

Numerous studies in cancer biology have provided evidence of the remarkable plasticity of cancer stem cells (CSCs). These cells play a key role in tumor initiation, metastasis, and resistance to treatment. One of the most critical features of CSCs is the epithelial-mesenchymal transition, which underlies their phenotypic plasticity. CSCs can modify their metabolic profile through interactions with cancer-associated fibroblasts, tumor-associated macrophages, and regulatory t-cells. CSCs creates a multifaceted cancerous environment that adapts to extensive changes in the secretome, variability of metabolic substrates and extracellular matrix composition. Intercellular communication is mediated though tumor-derived exosomes, carrying damage-associated molecular patterns. These metabolic shifts allow cancer cells to survive and function evading a hostile, immunosuppressive environment. It is important to summarize and integrate current knowledge on the links between cancer cell metabolism, CSCs plasticity, epithelial-mesenchymal transition, and immune regulation by regulatory T cells.