AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and metabolic reprogramming

• Published in: Translational oncology 2022-06, Vol.20, p.101421-101421, Article 101421
• Main Authors: Chang, Lin-Lin, Lu, Pei-Hua, Yang, Wei, Hu, Yan, Zheng, Lin, Zhao, Qiong, Lin, Neng-Ming, Zhang, Wen-Zhou
• Format: Article
• Language: English
• Subjects: AKR1C1; HIF-1α; Metabolic reprogramming; Original Research; Proliferation
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2022.101421

•AKR1C1 accelerates the proliferation of NSCLC cells.•AKR1C1 remodels metabolism in NSCLC cells.•HIF-1α may play a vital role in AKR1C1-mediated metabolic reprogramming. Non-small cell lung cancer (NSCLC) ranks first among cancer death worldwide. Despite efficacy and safety priority, targeted therapy only benefits ∼30% patients, leading to the unchanged survival rates for whole NSCLC patients. Metabolic reprogramming occurs to offer energy and intermediates for fuelling cancer cells proliferation. Thus, mechanistic insights into metabolic reprogramming may shed light upon NSCLC proliferation and find new proper targets for NSCLC treatment. Herein, we used loss- and gain-of-function experiments to uncover that highly expressed aldo-keto reductase family1 member C1 (AKR1C1) accelerated NSCLC cells proliferation via metabolic reprogramming. Further molecular profiling analyses demonstrated that AKR1C1 augmented the expression of hypoxia-inducible factor 1-alpha (HIF-1α), which could drive tumour metabolic reprogramming. What's more, AKR1C1 significantly correlated with HIF-1α signaling, which predicted poor prognosis for NSCLC patients. Collectively, our data display that AKR1C1 reprograms tumour metabolism to promote NSCLC cells proliferation by activating HIF-1α. These newly acquired data not only establish the specific role for AKR1C1 in metabolic reprogramming, but also hint to the possibility that AKR1C1 may be a new therapeutic target for NSCLC treatment. [Display omitted] In non-small cell lung cancer (NSCLC) cells, highly expressed aldo-keto reductase family1 member C1 (AKR1C1) accelerates proliferation of NSCLC cells involving in activation of hypoxia-inducible factor 1-alpha (HIF-1α) signalling, the latter of which could reprogram metabolism to fuel tumour proliferation. This study not only uncovers a novel role of AKR1C1 in metabolic reprogramming, but also highlights a possible target for AKR1C1-dominated NSCLC.