Nrf3: an emerging player in cancer, inflammation, and cellular homeostasis

Abstract

Nuclear factor erythroid 2-related factor 3 (Nrf3) is a transcription factor of the CNC-bZIP family that plays a critical role in managing cellular stress, redox balance, and internal homeostasis. Initially localized to the endoplasmic reticulum, Nrf3 undergoes a sophisticated activation process to reach the nucleus and regulate gene expression. Emerging evidence identifies Nrf3 as a multifaceted and context-dependent regulator whose biological impact varies significantly across different tissues and disease states. In cancer biology, Nrf3 exhibits a dual role by acting as either an oncogene or a tumor suppressor. In many malignancies, such as colorectal and pancreatic cancers, it promotes tumor growth by driving cell cycle progression, metabolic adaptation, and cancer cell survival. Conversely, in other contexts like breast cancer, Nrf3 can inhibit tumor progression by increasing stress signals and suppressing pathways that lead to cell migration. Beyond its role in oncology, Nrf3 coordinates responses to inflammation and metabolic shifts, often under the control of various cellular signals and microRNAs. This review highlights its importance in maintaining cellular health and underscores its potential as a clinical biomarker and therapeutic target, while calling for further research to fully clarify its diverse biological functions.