Figure 3.

EV modulation of mitochondria and its effects in the context of hallmarks of cancer. Cancer cells generate tumor-derived EVs (TEVs) that alter the mitochondrial behavior of different cell types of the tumor microenvironment to support cancer progression, invasion, and survival. Through these effects, TEVs are mediators of several of the hallmarks of cancer such as: (A) dysregulation of cellular energetics: cancer cells can induce the release of metabolites from CAFs and adipocytes to be used for cancer cell biosynthesis and FAO; (B) avoiding immune destruction: TEVs can induce immunosuppression by inducing M2 polarization in macrophages or T cell apoptosis via the mitochondrial intrinsic pathway; (C) promoting cell motility and facilitating invasiveness: increased FAO leads to an intracellular trafficking of mitochondria towards edge protrusions facilitating their migration. At the same time, they can induce mitochondrial apoptosis in endothelial barrier cells to permit intravasation; (D) resisting cell death: alterations in Bcl-2 family members leads to inhibition of mitochondrial apoptosis resulting in chemotherapy resistance and angiogenesis. Abbreviations used: OXPHOS: oxidative phosphorylation. TCA: tricarboxylic acid cycle. FAO: fatty acid metabolism. UCP1: uncoupling protein 1. MSC: mesenchymal stem cell. Labels in bold represent mitochondria-related elements and processes. The colors of the EVs reflect those of the parental cell that produced them. The colors of the text borders reflect the cells where the indicated processes take place. Figure created with BioRender.com (accessed on 31 March 2022).