Figure 1.

Origination of gastric tumor-initiating cells. A: Evidence suggests that the gastric stem cell (GSC) is one major origin of the gastric tumor-initiating cell (GATIC). GSCs exist in the isthmus and bottom of the gastric pit. Certain genetic, epigenetic, and/or environmental factors potentially transform these GSCs into malignant GATICs. For instance, Mist(+) and Villin(+) GSCs in the isthmus and Lgr5(+) GSCs in the bottom could act as the origins of GATICs through multiple signaling pathways; B: GATICs are also presumed to originate partially from bone marrow-derived cells (BMDCs). The recruitment of BMDCs to stomach by chemokines and other factors is in parallel with the multi-step progression of gastric cancer (GC), which lays the basis for the presumption that BMDCs undergo the malignant transformation into GATICs and promote GC development, the underlying mechanism of which requires further investigation.