Figure 1.

Education of CAF into a pro-tumorigenic phenotype by dying cancer cells. Mechanisms by which CAF can be transformed to a phenotype promoting tumorigenesis via the education of dying cancer cells. Cancer cells undergoing apoptosis secrete PGE2 which in turn can have pro-proliferative and immunosuppressive effects on surrounding cells in the TME. When cancer cells are exposed to cytotoxic therapies, they release DAMPs and ROS which stimulate CAF to differentiate into unfavorable phenotypes; upregulating pathways and secreting molecules associated with progression. Apoptotic cancer cells release EVs which have shown to be taken up by fibroblasts and educate them, resulting in CAF-promoting cancer cell metastasis.