Maintaining cancer stemness is the major role of FOXP4. A and B, GSEA demonstrated a positive correlation between FOXP4 and stem cell proliferation and upregulation. C, FOXP4 depletion compromises tumorsphere formation. D, RNA-seq revealed that various stemness markers were downregulated after knocking down YAP1 and FOXP4. E, scRNA-seq analysis demonstrated that YAP1/FOXP4 was co-upregulated with biological processes correlated with stem cell maintenance and proliferation. F and G, FOXP4 directly regulates SOX12 expression in gastric cancer, which was confirmed by the ChIP-qPCR assay. H and I, qRT-PCR and Western blot analysis of SOX12 expression in siFOXP4 transfectants. J and K, Both TCGA and ACRG cohorts demonstrated a positive association between FOXP4 and SOX12. TPM, transcript per million. ***, P < 0.001.