Figure 1.

Description of the origin of tumor development as the basis of cancer heterogeneity. (I) Non-malignant tumor cells secrete factors into the tumor microenvironment that promote UTSC division. (II) The TMB rate increases due to the rapid division of tumor cells. This process generates different cell phenotypes and induces heterogeneity. (III) Table showing the main types of non-malignant tumor cells and their specific paracrine factors that can act as mitogens on USTCs. (IV) Sankey diagram showing the relationships between specific paracrine mitogens from non-malignant tumor cells and the main cascades regulating USTC biological processes.