c-Myc,a key activator of cell proliferation and angiogenesis,promotes the development and progression of breast cancer.Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) is a multifunctional scaffold protein that suppresses the proliferation of breast cancer cells.In this study we investigated whether the cancer-suppressing effects of EBP50 resulted from its regulation of c-Myc signaling in human breast cancer MCF-7 cells in vitro and in vivo.We first found a significant correlation between EBP50 and c-Myc expression levels in breast cancer tissue,and demonstrated that EBP50 suppressed cell proliferation through decreasing the expression of c-Myc and its downstream proteins cyclin A,E and Cdc25A in MCF-7 cells.We further showed that EBP50 did not regulate c-Myc mRNA expression,but it promoted the degradation of c-Myc through the autophagic lysosomal pathway.Moreover,EBP50promoted integration between c-Myc and p62,an autophagic cargo protein,triggering the autophagic lysosomal degradation of c-Myc.In EBP50-silenced MCF-7 cells,activation of autophagy by Beclin-1 promoted the degradation of c-Myc and inhibited cell proliferation.These results demonstrate that the EBP50/Beclin-1/p62/c-Myc signaling pathway plays a role in the proliferation in MCF-7 breast cancer cells:EBP50 stimulates the autophagic lysosomal degradation of c-Myc,thereby inhibits the proliferation of MCF-7 cells.Based on our results,promoting the lysosomal degradation of c-Myc might be a promising new strategy for treating breast cancer.