Hierarchical heterogeneity in mammary tumors and its regulation by autophagy

ABSTRACT

Intra-tumor heterogeneity can be attributed in part to the ability of tumor cells to acquire traits associated with less differentiated cells. In MMTV-PyMT mammary tumors, this hierarchical heterogeneity can be illustrated with the use of ITGB1/CD29^hi ITGB3/CD61⁺ markers to enrich for mammary stem-like cells and ALDH⁺ to identify luminal progenitor-like cells. Macroautophagy/autophagy appears to be important for maintaining the cancer stem-like traits of both these populations. Interestingly, the regulation of these distinct cancer stem-like cells by autophagy occurs through EGFR-STAT3 and TGFB/TGF-β-SMAD pathways, respectively. These findings indicate that autophagy plays a significant role in cancer stem-like cells, and distinct cancer stem-like cells within a tumor may require different treatment modalities.

KEYWORDS:

• autophagy
• breast cancer
• cancer stem cell
• epigenetic
• heterogeneity