MeRIP and transcriptomal RNA sequencing revealed that METTL3 upregulates m6A modification in a large number of genes, including β-catenin destruction complex genes, such as APC. METTL3-enhanced APC mRNA m6A modification recruited YTHDF and elicited suppression of APC expression and subsequent enhanced expression of β-catenin, cyclin D1, c-Myc and c-Myc-regulated glycolytic genes, including PKM2. The reprogrammed expression of metabolic and cell cycle-promoting genes enhanced aerobic glycolysis, ESCC cell proliferation and tumour formation in mice (Fig. 8). Here, METTL3 is linked to esophageal squamous cell carcinoma.