The key initiator of ESCC is the transcription factor, SRY-box transcription factor 2 (Sox2) which has been found to cooperate with phosphorylated signal transducer and activator of transcription 3 (Stat3) to transform foregut basal keratin 5 positive progenitor cells (Figure 2B) [27,28]. This evidence concerns the gene STAT3 and esophageal squamous cell carcinoma.