SMAD4 and esophageal squamous cell carcinoma: Other notable genes relatively upregulated in SCC were GLI1, a downstream mediator of hedgehog signaling; SMAD4, which is involved in TGF-β signaling and is commonly is deleted in EAC and LUAD [4,5]; CCND1, a cyclin that is commonly amplified in ESCC [4]; and TWIST1, thought to be important in epithelial-to-mesenchymal transition [40].