Autophagy in different subtypes of breast cancer cells mediated by p-AMPK and its molecular mechanisms
- VernacularTitle:p-AMPK介导的不同亚型乳腺癌细胞自噬及其分子机制
- Author:
Xin-jiao YANG
1
;
Ru-yao HU
;
Zhe XIONG
;
Di ZOU
;
Jie CAI
;
Cong-long XIA
;
Zhong-bin BAI
;
Hong-ye ZHAO
Author Information
- Publication Type:Journal Article
- Keywords: p-AMPK; breast cancer; starvation induc-tion; estrogen receptor; autophagy; MTOR
- From: Chinese Pharmacological Bulletin 2025;41(5):898-907
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.
