J Cancer 2022; 13(8):2419-2429. doi:10.7150/jca.63152 This issue
Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, P.R.China
Shu Wang and Hui Zhang have contributed equally to this work and share first authorship
Purpose: Fuzzy planar cell polarity gene (FUZ) is regarded as a planar cell polarity effector that controls multiple cellular processes during vertebrate development. The role of FUZ in glucose metabolism, invasion, and metastasis of non-small cell lung cancer (NSCLC) is unclear. The aims of this study were to investigate the relationship between FUZ and glucose metabolism and its mechanism of action.
Materials and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to detect FUZ expression in A549 and H1299 cells. Additionally, qRT-PCR and western blot analysis were used to detect the expression of related glucose metabolism indicators, and lactate and 18 Fluorine fludeoxyglucose (18F-FDG) uptake assays used to detect changes in glucose metabolites. Further, cell invasion and migration behavior were evaluated by transwell and wound healing assays. In vivo tumor growth assay was conducted to assess the effect of FUZ.
Results: We found that FUZ was significantly upregulated in the NSCLC cell lines compared to that in the normal HBE cells. FUZ was found to promote energy metabolism through the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and overexpression of FUZ increased both lactic acid and 18F-FDG uptake. Moreover, FUZ knockdown significantly inhibited the migration and invasion of NSCLC cells. In vivo, FUZ knockdown can significantly inhibit tumor proliferation in the xenograft model, which was well identified by Micro-PET scan.
Conclusion: The present finding in vitro and vivo show that FUZ is involved in NSCLC cell energy metabolism, invasion and migration via the PI3K/AKT signaling pathway, suggesting that FUZ can be a potential therapeutic target for NSCLC.
Keywords: FUZ, NSCLC, glycolysis, migration, invasion