Mechanistically, PTTG1 depletion attenuated TGF-β, phosphorylated Smad2, and phosphorylated Smad3 levels, indicating inhibition of the TGF-β/Smad pathway.<h4>Conclusion</h4>PTTG1 promotes gastric cancer progression by activating the TGF-β/Smad axis to enhance cell proliferation, invasion, and EMT. Here, SMAD3 is linked to gastric cancer.