SLC2A1 boosts the resistance of non-small cell lung cancer to taxanes by stimulating the formation of EPCAM+ cancer stem-like cells via glycolysis

•SLC2A1 expression is increased in NSCLC tumor tissues, which correlated with a poorer prognosis.•SLC2A1 enhances NSCLC cell proliferation, invasion, migration, and chemo-resistance to taxanes.•SLC2A1 promotes the formation of EpCAM+ cancer stem like cells (CSCs) via activation of the glycolytic pathway.•SLC2A1+EpCAM+ CSCs exhibited chemo-resistant to taxanes compared to other cell subtypes.•SLC2A1low tumor cells promoted the function of CD8+t cells via HLA-A, HLA-B, and HLA-C, while SLC2A1low tumor cells suppressed the function of NK cells via HLA-E. The mechanisms by which SLC2A1 enhances chemo-resistance of taxanes to non-small cell lung cancer (NSCLC) remains enigmatic. An investigation into the SLC2A1 expression pattern and prognosis across diverse datasets, as well as our internally collected samples, was undertaken. Additionally, the biological function of SLC2A1 was further delved into through in vitro experiments. The study also examined the chemo-resistance of NSCLC to taxanes using CCK-8, Annexin-V, and caspase-3 assays. Furthermore, the impact of taxanes on SLC2A1 expression was determined via western blot analysis. The effects of SLC2A1 on the formation of CSCs was examined via flow cytometry and metabolomics techniques. Finally, the impact of SLC2A1 on the tumor microenvironment was analyzed using single-cell sequencing and cellchat. In the present investigation, it was observed that there was an elevated expression of SLC2A1 in NSCLC tumor tissues, which exhibited a significant association with a poorer prognosis. SLC2A1 overexpression in vitro promoted NSCLC cell proliferation, invasion, migration, chemo-resistance, and the formation of CD90+ and EpCAM+ CSCs. NSCLC cells were categorized based on SLC2A1 and EpCAM expression. SLC2A1highEpCAM+ CSCs were more chemo-resistance to taxanes. NSCLC patients with high SLC2A1 and EpCAM expression had poorer prognosis. Mechanically, SLC2A1 promoted the formation of CD90+ and EpCAM+ CSCs via activating glycolysis. Finally, SLC2A1low tumor cells promoted CD8+T cell function via HLA-A, B, C, and suppressed NK cell function via HLA-E. Together, SLC2A1 plays an important role in enhancing chemo-resistance of taxanes to NSCLC. [Display omitted]