In esophageal adenocarcinoma, tumor necrosis factor-α (TNF-α)-induced activation of the mammalian target of rapamycin (mTOR)-S6 kinase 1 (S6K1) pathway promotes GLI activity in an SMO-independent manner through phosphorylation of GLI1 [35]. The gene discussed is TNF; the disease is esophageal adenocarcinoma.