Metabolic reprogramming induced by inhibition of SLC2A1 suppresses tumor progression in lung adenocarcinoma

Lung adenocarcinoma (LAC) is one of the common reasons of cancer-related death with few biomarkers for diagnosis and prognosis. Solute carrier family 2 member 1 protein, SLC2A1, has been associated with tumor progression, metastasis, and poor prognosis in many human solid tumors. However, little is reported about its biological functions in lung adenocarcinoma. Here we observed a strong up-regulation of SLC2A1 in patients with LAC and found that SLC2A1 was significantly correlated with prognosis. Knockdown of SLC2A1 in LAC cells inhibits cellular proliferation and plate clone formation in vitro as well as suppression of glucose utilization. Meanwhile, silencing of SLC2A1 also suppresses tumor metastasis in vitro. Mechanistically, GSEA showed that genes in cell cycle pathway were prominently enriched in the higher SLC2A1 group. By a large-scale proteomic analysis, we revealed that cell cycle protein level was significantly increased in SLC2A1-high group. Collectively, our findings indicate that elevated SLC2A1 is a critical modulator in lung adenocarcinoma progression by altering glucose metabolism and the cell cycle pathway, and also suggest SLC2A1 as a promising target for lung adenocarcinoma therapy.