Consistently, we found both GRB2 levels and the activation levels of PI3K/AKT and ERK/MAPK pathways gradually increased in normal esophageal epithelium, atypical hyperplasia lesions and ESCC tumors in the 4-NQO-induced mouse model of ESCC (Fig. 5G). Here, GRB2 is linked to esophageal squamous cell carcinoma.