In pancreatic cancer, inactivation of CAFs disrupted stromal TGF-β signaling, leading to reduced TGF-β secretion, downregulation of Smad-mediated transcriptional activity and specificity protein 1 (Sp1) expression in tumor epithelial cells, suppression of downstream anti-apoptotic pathways (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and heat shock protein 70 (HSP70)), and ultimately a marked reduction in tumor growth and metastasis 105. Here, SP1 is linked to familial pancreatic carcinoma.