Table 1 Pro-oncogenic effects of cagA-positive H. pylori infection.

From: Molecular anatomy and pathogenic actions of Helicobacter pylori CagA that underpin gastric carcinogenesis

	Related cancer hallmarks	Pro-oncogenic actions	Molecular mechanisms	CagA dependency	Responsible factors	Reference no.
Cell autonomous pro-oncogenic actions	Sustained proliferative signaling	RAS-ERK signaling activation	Deregulation of SHP2	pY-CagA	EPIpYA-C/EPIpYA-D	⁹⁰
		Wnt signal activation	Complex with E-cadherin	CagA	CM motif	^{112, 113}
			Activation of cMet-PI3K-AKT signaling		CM motif	¹¹⁴
			Sequesteration of GSK3β		C-terminal region	¹¹⁵
			Degradation of RUNX3		−	^{116, 117}
	Growth suppressors	Degradation of RUNX3	−	CagA	−	^{116, 117}
		Degradation of p53	Complex with ASPP2		N-terminal region	^{124, 126}
		Degradation of p53	Activation of HDM2 and ARF-BP1		−	^{127, 128}
		Inactivation of p53	Ectopic expression of AID		−	¹³⁰
	Activate invasion and metastasis	Induction of hummingbird cell	Deregulation of SHP2	pY-CagA	EPIpYA-C/EPIpYA-D	^{70, 85, 91, 92}
		Perturbation of focal adhesion dynamics	Dregulation of SHP2-FAK signaling	pY-CagA	EPIpYA-C/EPIpYA-D	⁹¹
		Loss of apicobasal cell polarity	Inhibition of PAR1b	CagA	CM motif	^{104, 123}
		Tight junctional defect	Inhibition of PAR1b	CagA	CM motif	¹⁰⁴
		Adherence junctional defect	Complex with CRK	pY-CagA	Tyrosine phosphorylation	¹²⁰
		Altered stress fiber formation	Inhibition of PAR1b-GEF H1 signaling	CagA	CM motif	¹¹⁰
		Induction of transdifferentiation	Ectopic expression of CDX1 and CDX2		−	^{118, 119}
		EMT-like morphological change	Junctional and apicobasal polarity defects		−	^121,122,123
	Cell death	Resistant to apoptosis	Complex with ASPP2	CagA	N-terminal region	^{124, 126}
	Cell death	Promoting cell survival	Activation of MEK-ERK-MCL1 signaling	CagA	−	¹³⁴
	Genomic instability and mutation	Mitotic defects	Inhibition of PAR1b	CagA	CM motif	¹⁰⁹
		Hyper mutated phenotype	Ectopic expression of AID	CagA	−	¹³⁰
		Hyper mutated phenotype	CpG hypermethylation of MGMT	−	Potentiated by cagA	¹³³
		Induction of DNA double strand break	Inhibition of PAR1b	CagA	CM motif	¹³¹
		Induction of DNA double strand break	−	−	Potentiated by cagPAI	¹³²
Non-cell-autonomous pro-oncogenic actions	Induction of tumor-promoting inflammation	Sensitizing to NF-κB activation	Reduction of IκB in cells	CagA	CM motif	¹⁶⁶
		Activation of NF-κB	−		−	¹³⁰
			IKK activation via cMet-PI3K-AKT signaling		CM motif	¹¹⁴
			IKK activation via TAK1-TRAF6 signaling		−	¹⁶⁹
		Induction of IL-1β	Inflammasome activation in epithelial cells			¹⁶⁶
		Induction of IL-8	Activation of PI3K	pY-CagA	EPIpYA-B	¹⁴⁸
		Activation of STAT3	IL-6/gp130 signaling	CagA	pY independent	¹⁷⁰
		Activation of NF-κB	Activation of Nod1	−	Peptidoglycan	^{171, 172}
			Activation of ALPK1-TIFA signaling		ADP heptose	^174,175,176
			Activation of TLR2, TLR4 signaling		Lipopolysaccharide	¹⁷³
			Activation of NLRP3-inflammasome		cag PAI	^177,178,179

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Table 1 Pro-oncogenic effects of cagA-positive H. pylori infection.

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