Hierarchical heterogeneity in mammary tumors and its regulation by autophagy.
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/CD29hiITGB3/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.
a Department of Cancer Biology , University of Cincinnati College of Medicine , Cincinnati , OH , USA.
Syn Kok
SK
Yeo
a Department of Cancer Biology , University of Cincinnati College of Medicine , Cincinnati , OH , USA.
Jun-Lin
JL
Guan
D000818:Animals; D001343:Autophagy; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D008954:Models, Biological
autophagy; breast cancer; cancer stem cell; epigenetic; heterogeneity