Even though both control and Ptger4-KO tumor cells showed an increase in p-SMAD3 protein upon TGF-β and PGE2 exposure, EP4-deficient tumor cells had lower levels of p-SMAD3 compared with the controls, with and without treatment, indicating a deficiency in TGF-β signaling (Supplemental Figure 9B). This evidence concerns the gene SMAD3 and neoplasm.