Phosphorylation of ETS‐1 is a critical event in DNA polymerase iota‐induced invasion and metastasis of esophageal squamous cell carcinoma

An aberrantly elevated expression of DNA polymerase ι (Pol ι) is significantly associated with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC), yet the mechanisms behind this phenomenon remain obscure. Based on the RNA‐Seq transcriptome and real‐time PCR analysis, we identified ETS‐1 as a candidate gene involved in Pol ι‐mediated progression of ESCC. Wound‐healing and transwell assay indicated that downregulation of ETS‐1 attenuates Pol ι‐mediated invasiveness of ESCC. Signaling pathway analysis showed that Pol ι enhances ETS‐1 phosphorylation at threonine‐38 through the Erk signaling pathway in ESCC cells. Kaplan–Meier analysis, based on 93 clinical tissue samples, revealed that ETS‐1 phosphorylation at threonine‐38 is associated with poor prognosis of ESCC patients. The present study thus demonstrates that phosphorylation of ETS‐1 is a critical event in the Pol ι‐induced invasion and metastasis of ESCC.