SMAD4 and familial pancreatic carcinoma: For example, restoration of canonical TGF-β signaling in SMAD4-deficient pancreatic cancer cells (PCCs) has been reported to suppress angiogenesis by up-regulating anti-angiogenic thrombospondin-1 (THBS1) [62], and we detected a 5.63-fold increase in THBS1 in patients with a strong angiogenic signature.