Figure 1. Differences in Growth Signal Regulation between Normal and Tumorigenic Gastric Epithelium (IMAGE)
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Left: In normal gastric tissue, gastric epithelial cells rely on growth signals provided by the surrounding microenvironment. In particular, WNT signals — such as WNT2 secreted by neighboring cells — activate WNT signaling in gastric epithelial cells, allowing gastric stem cells to survive, self-renew, and continuously regenerate the stomach lining. Without this external WNT supply, normal gastric stem cells cannot maintain their function.
Right: In tumorigenic gastric tissue, cancer cells acquire genetic alterations that enable them to activate growth signals on their own, independent of the surrounding microenvironment. Gastric cancer cells can directly produce and secrete WNT ligands, allowing them to grow and proliferate without external support. This self-sustaining WNT activation arises either through MAPK pathway activation driven by KRAS or HER2 mutations, which induces secretion of the WNT ligand WNT7B, or through amplification of the WNT2 gene in gastric epithelial cells. As a result, gastric cancer cells become independent of external growth signals and gain the ability to sustain uncontrolled growth.
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Institute for Basic Science
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