AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and 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 fuel...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S193652332200081X |
| _version_ | 1818479464795865088 |
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| author | Lin-Lin Chang Pei-Hua Lu Wei Yang Yan Hu Lin Zheng Qiong Zhao Neng-Ming Lin Wen-Zhou Zhang |
| author_facet | Lin-Lin Chang Pei-Hua Lu Wei Yang Yan Hu Lin Zheng Qiong Zhao Neng-Ming Lin Wen-Zhou Zhang |
| author_sort | Lin-Lin Chang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T11:10:56Z |
| format | Article |
| id | doaj.art-cc7cf41081544dcfaf1daf726d021d81 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-10T11:10:56Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-cc7cf41081544dcfaf1daf726d021d812022-12-22T01:51:25ZengElsevierTranslational Oncology1936-52332022-06-0120101421AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and metabolic reprogrammingLin-Lin Chang0Pei-Hua Lu1Wei Yang2Yan Hu3Lin Zheng4Qiong Zhao5Neng-Ming Lin6Wen-Zhou Zhang7Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, ChinaDepartment of Medical Oncology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, ChinaDepartment 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, ChinaZhejiang University, Hangzhou, ChinaShulan International Medical College, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Hangzhou, ChinaKey Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No.261 Huansha Road, Hangzhou, Zhejiang 310006, China; Cancer Center, Zhejiang University, Hangzhou, China; Corresponding author at: Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No.261 Huansha Road, Hangzhou, Zhejiang 310006, China.Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China; Corresponding author at: Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China.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.http://www.sciencedirect.com/science/article/pii/S193652332200081XHIF-1αAKR1C1Metabolic reprogrammingProliferation |
| spellingShingle | Lin-Lin Chang Pei-Hua Lu Wei Yang Yan Hu Lin Zheng Qiong Zhao Neng-Ming Lin Wen-Zhou Zhang AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and metabolic reprogramming Translational Oncology HIF-1α AKR1C1 Metabolic reprogramming Proliferation |
| title | AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and metabolic reprogramming |
| title_full | AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and metabolic reprogramming |
| title_fullStr | AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and metabolic reprogramming |
| title_full_unstemmed | AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and metabolic reprogramming |
| title_short | AKR1C1 promotes non-small cell lung cancer proliferation via crosstalk between HIF-1α and metabolic reprogramming |
| title_sort | akr1c1 promotes non small cell lung cancer proliferation via crosstalk between hif 1α and metabolic reprogramming |
| topic | HIF-1α AKR1C1 Metabolic reprogramming Proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S193652332200081X |
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