Overall, using ESCC clinical samples, cell culture, xenograft models, Mettl1 conditional knockout and conditional knockin mice and in vivo ESCC initiation/progression models, we have demonstrated the strong physiological functions of METTL1/WDR4 mediated tRNA m7G modifications in selective oncogenic mRNA translation and ESCC progression. Here, METTL1 is linked to esophageal squamous cell carcinoma.