Nrf2 promotes oesophageal cancer cell proliferation via metabolic reprogramming and detoxification of reactive oxygen species

Cancer cells consume a large amount of energy and maintain high levels of anabolism to promote cell proliferation via metabolic reprogramming. Nuclear factor erythroid 2‐related factor 2 (Nrf2; NFE2L2) is a master transcription regulator of stress responses and promotes metabolic reprogramming to support cell proliferation in various types of cancer. As oesophageal cancer is one of the most aggressive gastrointestinal cancers, we aimed to clarify the effect of Nrf2 on metabolic reprogramming in oesophageal cancer. The relationship between Nrf2 expression and clinical outcome was evaluated using a database comprising 201 oesophageal cancers. Using in vitro assays and metabolome analysis, we examined the mechanism by which Nrf2 affects malignant phenotype. High‐level immunohistochemical expression of Nrf2 was significantly associated with poor recurrence‐free survival (HR = 2.67, p = 0.0004) and overall survival (HR = 2.90, p