On the other hand, in advanced pancreatic ductal adenocarcinomas (PDAC), intact TGF-β/SMAD4 pathway facilitates cancer progression; in advanced prostate cancer, bone-borne TGF-β induces osteoclastogenesis and bone metastasis by activating chemokine (C-X-C motif) receptor 4 (CXCR4) (Bardeesy et al., 2006; Zhang et al., 2021). The gene discussed is SMAD4; the disease is cancer.