SMAD4 and adenoma: Subsequent research identified that progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer in Lgr5+ gastric stem cells were accompanied with the deletion of Smad4 and Pten in the gastric antrum, while Smad4 and Pten deletions in differentiated cells (including antral pit, parietal and corpus Lgr5+ chief cells) failed to initiate tumor growth (Li et al., 2016).