Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Int J Biol Sci 2022; 18(11):4289-4300. doi:10.7150/ijbs.70002 This issue Cite

Research Paper

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

Chenyuan Li1*, Si Sun2*, Yi Tu1*, Hanpu Zhang1, Feng Yao1, Shichong Liao1, Shengrong Sun1✉, Zhiyu Li1✉, Zhong Wang1✉

1. Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.
2. Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.
*These authors contributed equally to this work.

✉ Corresponding authors: Zhong Wang, Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Road, Wuhan 430060, Hubei Province, P. R. China. Email: zhongwangchnedu.cn. ORCID: https://orcid.org/0000-0001-70 More

Citation:
Li C, Sun S, Tu Y, Zhang H, Yao F, Liao S, Sun S, Li Z, Wang Z. High Glucose Accelerates Tumor Progression by Regulating MEDAG-Mediated Autophagy Levels in Breast Cancer. Int J Biol Sci 2022; 18(11):4289-4300. doi:10.7150/ijbs.70002. https://www.ijbs.com/v18p4289.htm
Other styles

File import instruction

Abstract

Graphic 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 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 (MEDAGKD)-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 MEDAGKD cells. Treatment with the AMPK activator AICAR exhibited similar effects in MEDAG-overexpressing (MEDAGOE) 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.

Keywords: breast cancer, diabetes, MEDAG, EMT, AMPK signaling

Citation styles

APA
Li, C., Sun, S., Tu, Y., Zhang, H., Yao, F., Liao, S., Sun, S., Li, Z., Wang, Z. (2022). High Glucose Accelerates Tumor Progression by Regulating MEDAG-Mediated Autophagy Levels in Breast Cancer. International Journal of Biological Sciences, 18(11), 4289-4300. https://doi.org/10.7150/ijbs.70002.

ACS
Li, C.; Sun, S.; Tu, Y.; Zhang, H.; Yao, F.; Liao, S.; Sun, S.; Li, Z.; Wang, Z. High Glucose Accelerates Tumor Progression by Regulating MEDAG-Mediated Autophagy Levels in Breast Cancer. Int. J. Biol. Sci. 2022, 18 (11), 4289-4300. DOI: 10.7150/ijbs.70002.

NLM
Li C, Sun S, Tu Y, Zhang H, Yao F, Liao S, Sun S, Li Z, Wang Z. High Glucose Accelerates Tumor Progression by Regulating MEDAG-Mediated Autophagy Levels in Breast Cancer. Int J Biol Sci 2022; 18(11):4289-4300. doi:10.7150/ijbs.70002. https://www.ijbs.com/v18p4289.htm

CSE
Li C, Sun S, Tu Y, Zhang H, Yao F, Liao S, Sun S, Li Z, Wang Z. 2022. High Glucose Accelerates Tumor Progression by Regulating MEDAG-Mediated Autophagy Levels in Breast Cancer. Int J Biol Sci. 18(11):4289-4300.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use