Table 1.

Mechanisms of CagA-mediated gastric carcinogenesis.

Factors Involved	Mechanism	Outcomes	References
Induced EMT process	Cells undergoing EMT acquire cancer stem cell (CSC) properties	Enhances tumorigenesis	[89,90,91,92,93,94]
	Snail1 protein reduces the glycogen synthase kinase-3 (GSK-3) activity	Enhances carcinogenesis	[95]
YAP and TAZ	Failure in maintaining the organ size, tissue homeostasis, cell proliferation, and stem cell properties	Transformation of epithelial cells	[97,98,99,100]
Gastrokine 1 (GKN1)	CagA-induced activation of ERK pathway and AUF1 upregulation decreases the expression of GKN1	Induces cell cycle progression and inhibits apoptosis, causing invasion and metastasis of the gastric cancer cell	[103,104,105,106]
Apoptosis-stimulating protein p53 2	In association with CagA, disrupts the cellular polarity, damaging the mucosal barrier	Destroys the first-line defense mechanism causing survival of bacteria	[109]
Siva1 protein	Causes the activation of the PI3K/Akt pathway and XIAP E3 ubiquitin ligase	Tumorigenesis via the inhibition of apoptotic cell death, promoting the survival of damaged epithelial cells	[110]
Lrig1	Precise mechanism is unknown	Promotes gastric carcinogenesis	[111]
Heat shock protein 1 (HSP1)	CagA mediates downregulation of HSP1	Promotes persistent infection	[113,114]
Reg3	In association with CagA, alters the cell cycle, reducing its control on development	Gastric carcinogenesis	[115,116]
Caudal type homeobox 1 (CDX1)	CagA induces expression of CDX1, which promotes the cell proliferation and replacement of gastric epithelial cells with intestine-specific cells	Gastric carcinogenesis and failure of common gastric cancer chemotherapies	[117,118]
CD44v9-positive cancer stem-like cells	Protects the accumulated CagA after its translocation from autophagic degradation	Causes the reprogramming and de-differentiation of the cells into cancer progenitor cells	[95,126,127]