期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 18, 期 11, 页码 4289-4300出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.70002
关键词
breast cancer; diabetes; MEDAG; EMT; AMPK signaling
资金
- Fundamental Research Funds for the Central Universities [2042022kf1081]
- National Natural Science Foundation of China (NSFC) [81903166]
- Natural Science Foundation of Hubei Province [2020CFA026]
Recent studies have shown that diabetes is a major risk factor for breast cancer, but the mechanism is not fully understood. This study found a relationship between mesenteric estrogen-dependent adipogenesis and breast cancer under high glucose conditions, and the MEDAG-AMPK-autophagy axis plays a vital role in breast cancer progression in diabetic patients.
Recent studies have shown that diabetes is a major risk factor for breast cancer (BC), but the mechanism is incompletely understood. Mesenteric estrogen-dependent adipogenesis (MEDAG) plays a significant role in both glucose uptake and BC development. However, the relationship between MEDAG and BC under high glucose (HG) conditions remains unclear. In our study, MEDAG expression was higher in BC tissue from diabetic patients than in BC tissue from nondiabetic patients. HG promoted BC progression in vitro and in vivo by upregulating MEDAG expression. Furthermore, MEDAG deficiency increased the autophagosome number and autophagic flux. Moreover, inhibition of autophagy partially reversed MEDAG knockdown (MEDAG(KD))-induced suppression of tumorigenic biological behaviors and epithelial-mesenchymal transition (EMT) progression. Finally, MEDAG significantly suppressed AMPK phosphorylation. Additionally, the AMPK inhibitor Compound C markedly reduced autophagosome accumulation and antitumor effects in MEDAG(KD) cells. Treatment with the AMPK activator AICAR exhibited similar effects in MEDAG-overexpressing (MEDAG(OE)) cells. In conclusion, the MEDAG-AMPK-autophagy axis is vital to BC progression in diabetic patients. Our findings provide a novel treatment target for BC in patients with diabetes.
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