PGK1 promotes NSCLC progression by enhancing aerobic glycolysis and activating the AKT/ERK signaling pathway

Backgrounds : Metabolic reprogramming, especially aerobic glycolysis, is considered a hallmark of cancer and is becoming a novel target for cancer therapy. Phosphoglycerate kinase I (PGK1), an important enzyme that generates the first ATP in the glycolysis pathway, has already shown aberrant expression in various cancers. Methods : After analyzing the patient's cancer tissue sample data, we mainly validate the experimental conclusions at the cellular and animal levels. Results : This study uncovered that PGK1 plays a key role in non-small cell lung cancer (NSCLC) development and progression. We found that PGK1 was highly expressed in non-small cell lung cancer tissues; its expression was positively correlated with tumor grade and clinical stage and negatively correlated with patients' overall survival. Importantly, its expression was associated with the clinicopathological characteristics of lung cancer patients. Overexpression of PGK1 promoted lung tumor cell migration/proliferation both in vitro and in vivo. Mechanistically, PGK1 promotes NSCLC development and progression by activating the AKT/ERK signaling pathway and altering the aerobic glycolysis pathway. PGK1 was a downstream target gene of HIF1α and plays an essential role in the hypoxia-induced metastasis of NSCLC. In addition, PGK1 expression was positively correlated with HIF1α expression in NSCLC tissues. Conclusion : Therefore, we concluded that PGK1 could be a biomarker for NSCLC diagnosis and outcome evaluation, and targeting PGK1 should be an innovative strategy for NSCLC therapy in the future.