A chief source of cancer and repair in stomachs

Abstract

Differentiated cells had long been thought to be non‐dividing, though we now know many can proliferate after injury. A new study by Leushacke et al (2017) shows how injury recruits mature, Lgr5‐expressing gastric chief cells to become stem cells that can either regenerate damaged tissue or fuel precancerous lesions.

Figure 1. Lgr5‐expressing chief cells in the gastric corpus can repair the stomach and are sources of metaplasia and precancerous lesions after injury

At homeostasis, Lgr5‐expressing chief cells remain in the base of the corpus unit and are not proliferative, while active stem cells in the isthmus give rise to all other epithelial cell types. However, after metaplasia‐inducing injury (as can be induced in the laboratory setting with high doses of tamoxifen; Huh et al, 2012), Lgr5‐expressing, “reserve” stem cells in the bottom part of the gland activate Wnt signaling, become metaplastic, and re‐enter the cell cycle in a reprogramming event. Without incurring additional damage, Lgr5‐expressing cells have potential to generate all epithelial cells in the gastric gland. If chief cells acquire oncogenic mutations (e.g., activate Ras; Choi et al, 2016), they can form dysplastic lesions, thus being a precursor cell to gastric cancer formation.