High Glucose Accelerates Tumor Progression by Regulating MEDAG-Mediated Autophagy Levels in Breast Cancer

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2022 Jul 22

PMID 35864962

Authors

Chenyuan Li

Si Sun

Yi Tu

Hanpu Zhang

Feng Yao

Shichong Liao

Shengrong Sun

Zhiyu Li

Zhong Wang

Affiliations

Soon will be listed here.

Abstract

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 and by upregulating MEDAG expression. Furthermore, MEDAG deficiency increased the autophagosome number and autophagic flux. Moreover, inhibition of autophagy partially reversed MEDAG knockdown (MEDAG)-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 cells. Treatment with the AMPK activator AICAR exhibited similar effects in MEDAG-overexpressing (MEDAG) 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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