Evidence-Based Complementary and Alternative Medicine

Review Article

Physiological Significance of Ion Transporters and Channels in the Stomach and Pathophysiological Relevance in Gastric Cancer

Table 1

Expression, localization, and physiological and pathophysiological functions of ion transporters in the normal gastric epithelium and GC.


Ions	Related transporters	Human gene symbol	Parietal localization	Transporter type	Physiological role in gastric acid secretion	Pathophysiological relevance in GC

Cl⁻	CFTR	ABCC7	Apical	O	Pumps Cl⁻ out of parietal cells to form HCl with H⁺	CFTR expression is upregulated in GC [23] and is closely related to CA199 [24].
	CLC-2	CLCN2	Apical	O	Pumps Cl⁻ out of parietal cells to form HCl with H⁺	Loss of CLC-2 influences acid secretion and causes precancerous changes [25].
	CLIC-6	CLIC6	Apical	O	Pumps Cl⁻ out of parietal cells to form HCl with H⁺

H⁺	NHE1	SLC9A1	Basolateral	E	Na⁺-H⁺ exchanger pumps out redundant H⁺ and pumps in Na⁺ at the basolateral side	NHE1 expression is upregulated in GC, and functional data show that loss of NHE1 inhibits GC cell proliferation, migration, and invasion [26].
	NHE2	SLC9A2	Basolateral	E
	NHE4	SLC9A4	Basolateral	E

K⁺	KCNQ1	KCNQ1	Apical	O	Pumps K⁺ into the lumen	KCNQ1 is implicated in GC progression [27, 28].
	Kir2.2/4.1/5.1	KIR	Apical	O	Pumps K⁺ into the lumen	Kir2.2 plays a role in the escape of cancer cells from premature senescence and in tumor formation [29].
	Kv1.5/4.1/7.1/11.1	KCNA/D/Q/H	Apical	O	Pumps K⁺ into the lumen	Kv1.5/4.1/7.1/11.1 promotes GC cell proliferation and progression [27, 28, 30–32].
	NKCC1	SLC12A2	Basolateral	C	Na⁺-K⁺-2Cl⁻ cotransporter pumps Na⁺, K⁺, and 2Cl⁻ into parietal cells

	AE1	SLC4A1	Basolateral	E	Cl⁻- exchanger pumps Cl⁻ into and out of parietal cells	AE1 may function as an oncogene in GC [33].
	AE2	SLC4A2	Basolateral	E	Cl⁻- exchanger pumps Cl⁻ into and out of parietal cells	The cytoplasmic AE1/p16 complex plays a key role in GC progression [33–35].
	SLC26A7	SLC26A7	Basolateral	E	Cl⁻- exchanger pumps Cl⁻ into and out of parietal cells	AE2 may play a role in carcinogenesis [36–38].
	NBCe1	SLC4A4	Basolateral	C	Na⁺- cotransporter pumps Na⁺ and out of parietal cells

C: cotransporter; E: exchanger; O: orphan transporter.