Figure 9: Schematic representation of the proposed mechanism of ACh-modulated M3/EGFR pathway in gastric cancer. | Scientific Reports

Figure 9: Schematic representation of the proposed mechanism of ACh-modulated M3/EGFR pathway in gastric cancer.

From: Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation

Figure 9

(a) In gastric cancer cells, cytoplasm ChAT protein catalyzes ACh synthesis, then ACh is secreted and released into the extracellular space, the extracellular ACh could combine and activate M3 receptor located in cytomembrane of cells, following activating EGFR signaling, and then leading to the increasement of p-ERK1/2 and p-AKT, thus, promote gastric cancer cell proliferation and survival. (b) When the function of M3R was blocked by specific antagonists (such as 4-DAMP), or its downstream effector EGFR, inhibited by specific inhibitor AG1478, the auto-stimulating role of ACh in cell proliferation will be weaken in some degree. The M3R/EGFR signaling inhibitors can enhance the chemosensitivity of 5-Fu and reduce cell viability in gastric cancer. The combined strategy may provide a feasible strategy for gastric cancer therapy.

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