Affinity pull-down followed by mass spectrometry revealed that Smad4, the central intracellular mediator of transforming growth factor-β/Smad (TGF-β/Smad) signaling, which is a key pathway in cancer invasion and metastasis, was one of the proteins associated with circPTEN1 with the highest abundance (Fig. 4A, Supplementary Fig. 8A and B). The gene discussed is SMAD4; the disease is cancer.