EBP50 suppresses the proliferation of MCF-7 human breast cancer cells via promoting Beclin-1/p62- mediated lysosomal degradation of c-Myc

Authors: Hong LIU1, Wu-li ZHAO1, Jia-ping WANG2, Bing-mu XIN2, Rong-guang SHAO1
1 Key Laboratory of Biotechnology of Antibiotics of National Health and Family Planning Commission (NHFPC), Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China
2 China Astronaut Research and Training Centre, Beijing 100094, China
Corresponding to: Rong-guang SHAO:,
DOI: 10.1038/aps.2017.171
Received: 21 July 2017
Accepted: 8 November 2017
Advance online: 28 December 2017


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, EBP50 promoted 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.
Keywords: human breast cancer; MCF-7 cells; c-Myc signaling; protein stability; protein interaction; autophagy lysosomal degradation