MSCs promote stemness and chemoresistance in gastric cancer (GC) cells through fatty acid oxidation (FAO). TGF-β1 secreted by MSCs activates SMAD2/3 through TGF-β receptors, which then induce lncRNA MACC1-AS1 expression in GC cells and promote FAO-dependent stemness and chemoresistance through antagonizing miR145-5p. Pharmacologic inhibition of FAO with etomoxir (ETX) attenuates MSC-induced FOLFOX regiment resistance in vivo. This evidence concerns the gene SMAD2 and gastric cancer.