AKR1C1 expression is induced by hexavalent chromium exposure and lung squamous carcinoma development for mediating...

Lung squamous cell carcinoma (LUSC) is strongly associated with environmental and occupational carcinogen exposure. The early molecular events driving metabolic adaptation and malignant progression in LUSC remain incompletely understood. In this study, we demonstrated that AKR1C1 expression was markedly elevated during LUSC progression and in carcinogen-exposed epithelial models. Functional analyses revealed that AKR1C1 promoted early tumor-associated phenotypes by directly regulating FASN. AKR1C1 activation drived lipid metabolic dysregulation characterized by enhanced fatty acid synthesis, thereby facilitating metabolic adaptation and survival during early LUSC carcinogenesis. Collectively, our findings identified AKR1C1 as an early-response biomarker and a pivotal metabolic node controlling FASN-dependent lipid metabolic reprogramming in LUSC.