SMAD2 and pancreatic neoplasm: Overexpressed NR5A2 directly binds to the promoter region of the GDF-15 gene and thus enhances the transcription of GDF-15 in pancreatic cancer and promotes the progression of pancreatic cancer.[44] SULF2, an extracellular component whose high expression in pancreatic tissues or serum promotes pancreatic cancer growth and metastasis and correlates with a poor prognosis, was found to act through the activation of the TGFβ-SMAD2/3 pathway in pancreatic ductal carcinoma by GDF15.[45,46] In the past few years, the mechanism of GDF-15 in other cancers has also been investigated.