SMAD4 and cancer: Autophagy inhibition promotes EMT, invasion, and metastasis in many cancer cells, including gastric, colorectal, melanoma, and pancreatic cancer cells, mouse embryonic fibroblasts, and keratinocytes.293–295 By contrast, TGF-β–induced autophagy promotes cancer cell migration via MAPK–ERK activation in NSCLC and SMAD4-negative pancreatic cancer cells.296,297 However, autophagy inhibits metastasis in HCC298 and prevents EMT in breast and SMAD4-positive pancreatic cancer cells.297,299