Autophagy is essential for the endothelial differentiation of breast cancer stem-like cells

Blood vessels serve an important role in tumor growth and metastasis, and recent studies have shown that certain tumor cancer stem cells may differentiate into endothelial cells and contribute to angiogenesis. In the present study, vascular endothelial growth factor (VEGF) was used to induce endothelial differentiation of breast cancer stem-like cells (BCSLCs), and methods including flow cytometry, western blotting and immunofluorescence were used to study the relationship between autophagy and the endothelial differentiation of BCSLCs. The results showed that BCSLCs could differentiate into endothelial cells under the induction of VEGF in vitro. Subsequently, the role of autophagy in the endothelial differentiation of BCSLCs was examined. Autophagic activity was measured during endothelial differentiation of BCSLCs, and the association between autophagy and endothelial differentiation was investigated using autophagy activators, autophagy inhibitors and autophagy related 5 (Atg5)-knockdown BCSLCs. Autophagy was increased during endothelial differentiation of BCSLCs, and there was a positive association between autophagy and endothelial differentiation. The ability of cells to undergo endothelial differentiation was reduced in BCSLCs with Atg5 knockdown. Therefore, autophagy was essential for endothelial differentiation of BCSLCs, and the findings of the present study may highlight novel potential avenues for reducing angiogenesis and improving treatment of breast cancer.