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

Technol Cancer Res Treat. 2023 Jan-Dec:22:15330338231161141. doi: 10.1177/15330338231161141.

Abstract

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.

Keywords: EMT; NRF1; OXPHOS; ROS; anoikis; breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Anoikis* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Homeostasis
  • Humans
  • Membrane Potential, Mitochondrial
  • Mitochondria / metabolism
  • Nuclear Respiratory Factor 1* / genetics
  • Nuclear Respiratory Factor 1* / metabolism
  • Oxidative Phosphorylation
  • Reactive Oxygen Species / metabolism

Substances

  • NRF1 protein, human
  • Nuclear Respiratory Factor 1
  • Adenosine Triphosphate
  • Reactive Oxygen Species