In summary, to the best of our knowledge, this study is the first to reveal the oncogenic role of CST1 in ESCC by enhancing mitochondrial respiratory chain complex I enzyme activity to mediate the OXPHOS/MEK/ERK axis responsible for cell migration and invasion (Fig. 10), suggesting that CST1/OXPHOS might be a promising target for ESCC treatment. Here, CST1 is linked to esophageal squamous cell carcinoma.