NRF1 Regulates the Epithelial Mesenchymal Transition of Breast Cancer by Modulating ROS Homeostasis

Autor: Linjuan Sun BS, Nan Ouyang BS, Shaheryar Shafi MS, Rongchuan Zhao BS, Jinlin Pan BS, Lei Hong MS, Xueyan Song MS, Xiaohan Sa BS, Yuanshuai Zhou PhD
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Technology in Cancer Research & Treatment, Vol 22 (2023)
Druh dokumentu: article
ISSN: 1533-0338
15330338
DOI: 10.1177/15330338231161141
Popis: Introduction: Nuclear respiratory factor 1 (NRF1) is an important regulator involved in mitochondrial biogenesis and energy metabolism. However, the specific mechanism of NRF1 in anoikis and epithelial-mesenchymal transition (EMT) remains unclear. Methods: We examined the effect of NRF1 on mitochondria and identified the specific mechanism through transcriptome sequencing, and explored the relationships among NRF1, anoikis, and EMT. Results: We found that upregulated NRF1 expression led to increased mitochondrial oxidative phosphorylation (OXPHOS) and ATP generation. Simultaneously, a significant amount of ROS is generated during OXPHOS. Alternatively, NRF1 upregulates the expression of ROS-scavenging enzymes, allowing tumor cells to maintain low ROS levels and promoting anoikis resistance and EMT. We also found that exogenous ROS was maintained at a low level by NRF1 in breast cancer cells. Conclusion: our study provides mechanistic insight into the function of NRF1 in breast cancer, indicating that NRF1 may serve as a therapeutic target for breast cancer treatment.
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