SMAD3 and neoplasm: In addition, in tumor cells, increasing evidence has revealed the connections among HIF-1α, TGF-β/SMAD3 signaling and glycolysis: TGF-β signaling inhibits glycolysis under normoxic conditions but significantly promotes glycolysis under hypoxic conditions in tumor cells in vitro and in vivo, and SMAD3 plays a key role in the metabolic reprogramming associated with tumor progression, including tumor glycolysis [46], glutaminolysis [2], and lipid metabolism [20].