2. Academic Validation
  3. Gankyrin modulated non-small cell lung cancer progression via glycolysis metabolism in a YAP1-dependent manner

Gankyrin modulated non-small cell lung cancer progression via glycolysis metabolism in a YAP1-dependent manner

  • Cell Death Discov. 2022 Jul 9;8(1):312. doi: 10.1038/s41420-022-01104-3.
Tong Yu  # 1 2 3,  Yanyan Liu  # 4,  Junwen Xue  # 2,  Xiang Sun 2,  Di Zhu 2,  Lu Ma 2,  Yingying Guo 2,  Tongzhu Jin 2,  Huiying Cao 2,  Yingzhun Chen 5,  Tong Zhu 6,  Xuelian Li 2,  Haihai Liang 2 3,  Zhimin Du 7 8,  Hongli Shan 9 10 11
Affiliations

Affiliations

  • 1 Shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai, 201620, P. R. China.
  • 2 Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, P. R. China.
  • 3 Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin, Heilongjiang, 150081, P. R. China.
  • 4 Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, Guangdong, 519000, P. R. China.
  • 5 Department of Pathology, the Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, P. R. China.
  • 6 Department of General Surgery, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, P. R. China.
  • 7 Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, Guangdong, 519000, P. R. China. dzm1956@126.com.
  • 8 Institute of Clinical Pharmacy, the Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, P. R. China. dzm1956@126.com.
  • 9 Shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai, 201620, P. R. China. shanhl@sues.edu.cn.
  • 10 Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, P. R. China. shanhl@sues.edu.cn.
  • 11 Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin, Heilongjiang, 150081, P. R. China. shanhl@sues.edu.cn.
  • # Contributed equally.
PMID: 35810157 DOI: 10.1038/s41420-022-01104-3
Abstract

Non-small cell lung Cancer (NSCLC) is highly malignant and heterogeneous form of lung Cancer and involves various oncogene alterations. Glycolysis, an important step in tumor metabolism, is closely related to Cancer progression. In this study, we investigated the biological function and mechanism of action of Gankyrin in glycolysis and its association with NSCLC. Analyzed of data from The Cancer Genome Atlas as well as NSCLC specimens and adjacent tissues demonstrated that Gankyrin expression was upregulated in NSCLC tissues compared to adjacent normal tissues. Gankyrin was found to significantly aggravate cancer-related phenotypes, including cell viability, migration, invasion, and epithelial mesenchymal transition (EMT), whereas Gankyrin silencing alleviated the malignant phenotype of NSCLC cells. Our results reveal that Gankyrin exerted its function by regulating YAP1 expression and increasing its nuclear translocation. Importantly, YAP1 actuates glycolysis, which involves glucose uptake, lactic acid production, and ATP generation and thus might contribute to the tumorigenic effect of Gankyrin. Furthermore, the Gankyrin-accelerated glycolysis in NSCLC cells was reversed by YAP1 deficiency. Gankyrin knockdown reduced A549 cell tumorigenesis and EMT and decreased YAP1 expression in a subcutaneous xenograft nude mouse model. In conclusion, both Gankyrin and YAP1 play important roles in tumor metabolism, and Gankyrin-targeted inhibition may be a potential anti-cancer therapeutic strategy for NSCLC.

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