| First Author | Yeo SK | Year | 2016 |
| Journal | Cancer Res | Volume | 76 |
| Issue | 11 | Pages | 3397-410 |
| PubMed ID | 27197172 | Mgi Jnum | J:232037 |
| Mgi Id | MGI:5775837 | Doi | 10.1158/0008-5472.CAN-15-2946 |
| Citation | Yeo SK, et al. (2016) Autophagy Differentially Regulates Distinct Breast Cancer Stem-like Cells in Murine Models via EGFR/Stat3 and Tgfbeta/Smad Signaling. Cancer Res 76(11):3397-410 |
| abstractText | Cancer stem-like cells contribute to tumor heterogeneity and have been implicated in disease relapse and drug resistance. Here we show the coexistence of distinct breast cancer stem-like cells (BCSC) as identified by ALDH(+) and CD29(hi)CD61(+) markers, respectively, in murine models of breast cancer. While both BCSC exhibit enhanced tumor-initiating potential, CD29(hi)CD61(+) BCSC displayed increased invasive abilities and higher expression of epithelial-to-mesenchymal transition and mammary stem cell-associated genes, whereas ALDH(+) BCSC were more closely associated with luminal progenitors. Attenuating the autophagy regulator FIP200 diminished the tumor-initiating properties of both ALDH(+) and CD29(hi)CD61(+) BCSC, as achieved by impairing either the Stat3 or TGFbeta/Smad pathways, respectively. Furthermore, combining the Stat3 inhibitor Stattic and the Tgfbeta-R1 inhibitor LY-2157299 inhibited the formation of both epithelial and mesenchymal BCSC colonies. In vivo, this combination treatment was sufficient to limit tumor growth and reduce BCSC number. Overall, our findings reveal a differential dependence of heterogeneous BCSC populations on divergent signaling pathways, with implications on how to tailor drug combinations to improve therapeutic efficacy. Cancer Res; 76(11); 3397-410. (c)2016 AACR. |
