We previously demonstrated that hypoxia selectively increases the phosphorylation of SMAD3 (pSMAD3) in the HT-1080 cancer cell line, a process that was required for the hypoxia-induced increase in cancer cell invasion [37], suggesting that hypoxia induces a pSMAD equilibrium bias that might contribute to the shift in TGFβ signaling from the anti-tumorigenic to the pro-tumorigenic state. This evidence concerns the gene SMAD3 and cancer.