Nrf3 promotes the proliferation and migration of triple‑negative breast cancer by activating PI3K/AKT/mTOR and epithelial‑mesenchymal transition

Wan-Meng Chen; Qing-Yong Hu; Wei Hou; Meng-Wei Chen; Ya-Hui Chen; Jian-Cai Tang

doi:10.3892/ol.2023.14030

Nrf3 promotes the proliferation and migration of triple‑negative breast cancer by activating PI3K/AKT/mTOR and epithelial‑mesenchymal transition

Oncol Lett. 2023 Aug 28;26(4):443. doi: 10.3892/ol.2023.14030. eCollection 2023 Oct.

Authors

Wan-Meng Chen¹, Qing-Yong Hu¹, Wei Hou¹, Meng-Wei Chen¹, Ya-Hui Chen¹, Jian-Cai Tang¹

Affiliation

¹ Department of Biochemistry, Institute of Basic Medicine and Forensics Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.

Abstract

Nuclear factor erythroid 2-related factor 3 (Nrf3) is increasingly implicated in multiple types of cancer; however, its function in triple-negative breast cancer (TNBC) remains unclear. This study aimed to examine the role of Nrf3 in TNBC. Compared with adjacent normal tissues, TNBC tissues expressed higher levels of Nrf3, and its expression was negatively correlated with survival time. Additionally, Nrf3 knockdown reduced the proliferation and migration of TNBC cells, whereas overexpression of Nrf3 had the opposite effects in vitro and in vivo. Moreover, functional enrichment of TNBC cells overexpressing Nrf3 allowed for the identification of numerous genes and pathways that were altered following Nrf3 overexpression. Further study showed that overexpression of Nrf3 activated the PI3K/AKT/mTOR signaling pathway and regulated the expression of proteins associated with epithelial-mesenchymal transition. Nrf3 was found to directly bind to p110α promoter regions, as evidenced by luciferase reporter and chromatin immunoprecipitation assays. Furthermore, PI3K inhibitors partially decreased the proliferation and migration of the Nrf3 overexpressing TNBC cells. In conclusion, Nrf3 enhances cellular proliferation and migration by activating PI3K/AKT/mTOR signaling pathways, highlighting a novel therapeutic target for TNBC.

Keywords: PI3K/Akt/mTOR; epithelial-mesenchymal transition; nuclear factor erythroid 2-related factor 3; proliferation and migration; triple-negative breast cancer.

Grants and funding

This study was supported by the Strategic Cooperation Research Project of Nan Chong (grant no. 20SXCXTD004) and the Major Emphasis Project of North of Sichuan Medical College (grant no. CBY22-ZDA02, CBY22-ZD04).