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

Translational Oncology

Lin Zheng¹  Pei-Hua Lu¹  Wei Yang²  Qiong Zhao³  Yan Hu⁴  Lin-Lin Chang⁴  Wen-Zhou Zhang⁵  Neng-Ming Lin⁶ 

[1] Henan Cancer Hospital, Zhengzhou 450008, China;Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China;Department of Pharmacy, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China;;Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University &Shulan International Medical College, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Hangzhou, China;Zhejiang University, Hangzhou, China;

关键词: HIF-1α;    AKR1C1;    Metabolic reprogramming;    Proliferation;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown