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

• Published in: Cell death discovery Vol. 8; no. 1; p. 312
• Main Authors: Yu, Tong, Liu, Yanyan, Xue, Junwen, Sun, Xiang, Zhu, Di, Ma, Lu, Guo, Yingying, Jin, Tongzhu, Cao, Huiying, Chen, Yingzhun, Zhu, Tong, Li, Xuelian, Liang, Haihai, Du, Zhimin, Shan, Hongli
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.07.2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/67/1612/1350; 631/67/395; Acid production; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Cycle Analysis; Cell migration; Cell viability; Genomes; Glycolysis; Lactic acid; Life Sciences; Lung cancer; Mesenchyme; Metabolism; Non-small cell lung carcinoma; Nuclear transport; Phenotypes; Small cell lung carcinoma; Stem Cells; Tumorigenesis; Xenografts; Yes-associated protein
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-022-01104-3

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.