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TGF‑β1‑induced epithelial‑mesenchymal transition increases fatty acid oxidation and OXPHOS activity via the p‑AMPK pathway in breast cancer cells.

Abstract：

:Breast cancer is the most common malignancy in women, and metastasis is the leading cause of death in breast cancer patients. Previous studies have shown that epithelial‑mesenchymal transition (EMT) is involved in the metastasis of breast cancer, but the metabolic reprogramming and regulation mechanisms involved in the EMT process are still unclear. In the present study, we successfully constructed an EMT cell model induced by transforming growth factor β1 (TGF‑β1) treatment of MCF‑7 cells at different times. The results showed that cell adhesion decreased, cell invasion increased and ATP levels increased in EMT MCF‑7 cells treated with TGF‑β1. Furthermore, the expression of fatty acid synthase (FASN) was decreased, and the expression of key fatty acid β‑oxidation enzymes (CPT1 and CD36) was elevated in treated cells compared to control cells. These results showed that the fatty acid oxidation pathway was enhanced. In addition, the expression of NADH:ubiquinone oxidoreductase subunit B8 (NDUFB8), mitochondrial transcription factor A (TFAM) and cytochrome c oxidase subunit I (COXI) increased, and the mitochondrial DNA copy number and ROS levels were also significantly increased during TGF‑β1‑induced EMT. These results indicated that mitochondrial oxidative phosphorylation (OXPHOS) activity was enhanced during EMT. In addition, we observed that the expression of p‑AMPK was increased and ACC (Acetyl‑CoA Carboxylase) was decreased during TGF‑β1‑induced EMT in MCF‑7 cells. Immunohistochemical analysis of clinical samples revealed high expression of FASN in epithelial cells that had high expression of E‑cadherin, while high expression of CPT‑1 was observed in mesenchymal cells that had high expression of vimentin. Results of the current study showed a metabolic transition in TGF‑β1‑induced EMT in MCF‑7 cells. This transition may regulate fatty acid oxidation and OXPHOS activity in EMT MCF‑7 cells through the p‑AMPK pathway. These data suggest that a metabolic transition that suppresses lipogenesis and favors energy production is an essential component of TGF‑β1‑induced EMT and metastasis in breast cancer. This study thus provides a new strategy for identifying new therapeutic targets for breast cancer.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Liu QQ,Huo HY,Ao S,Liu T,Yang L,Fei ZY,Zhang ZQ,Ding L,Cui QH,Lin J,Yu M,Xiong W

doi

10.3892/or.2020.7661

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

1206-1215

issue

eissn

1021-335X

issn

1791-2431

journal_volume

pub_type

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TGF‑β1‑induced epithelial‑mesenchymal transition increases fatty acid oxidation and OXPHOS activity via the p‑AMPK pathway in breast cancer cells.