In summary, to the best of our knowledge, this study is the first to unveil the carcinogenic role of CST1 on ESCC by activating the MEK/ERK/CREB pathway to promote cell migration and invasion, and the regulatory effect of miR-942-5p on targeting CST1, suggesting that miR-942-5p/CST1 axis might be a promising target for diagnosis and treatment of ESCC. Here, MAP2K7 is linked to esophageal squamous cell carcinoma.