Cancer stem cell plasticity and tumor hierarchy

Figure 1 Schematic of unified model of clonal evolution and cancer stem cells. The proposed unified model depends on dynamic hierarchical organization and clonal mutations for tumor heterogeneity. In this depiction, the originating CSC that sustained the first oncogenic mutation gives rise to subclones with self-renewal capabilities that accumulate epigenetic and genetic changes over time. Each different CSC subclone gives rise to intermediate transit-amplifying progenitors that lack self-renewal capabilities. A subset of these progenitors (shown in green) follows a model of tumor cell plasticity and bidirectional conversion between non-CSC to CSC states. This phenotypic change is modulated by microenvironmental stimuli which confer CSC self-renewal capacities to the differentiated cell. CSC: Cancer stem cell.