Hierarchical heterogeneity in mammary tumors and its regulation by autophagy

Figures & data

Figure 1. Illustration of heterogeneity within mammary tumors with ITGB1^hi ITGB3⁺ CSCs (red), ALDH⁺ CSCs (green) and bulk tumor cells (white). The model shows that ITGB1^hi ITGB3⁺ CSCs are more mammary stem cell-like and at the top of the hierarchy within the epigenetic landscape (adapted from Conrad Waddington). ALDH⁺ CSCs, which are luminal progenitor-like, occupy an intermediate epigenetic state followed by bulk tumor cells at the bottom. ITGB1^hi ITGB3⁺ CSCs are more dependent on TGFB-SMAD signaling, whereas ALDH⁺ CSCs are reliant on EGFR-STAT3. Both these pathways are regulated by autophagy and RB1CC1, highlighting an important role for this process in CSCs.