Role of ion channels in gastrointestinal cancer

Table 3 Calcium channels

Gene name (s)	Cancer	Role	Functional activity
TRPC1	Colorectal	Oncogene	Expression up-regulated; promotes metastasis[5,256,274]
	Esophageal	Oncogene	Expression up-regulated[275]
	Gastric	Oncogene	Expression up-regulated[276]
	Hepatocellular	Oncogene	Expression up-regulated[249]
TRPC6	Esophageal	Oncogene	Expression up-regulated; necessary for Ca2+ increase to promote G2 progression; associated with tumor stage and poor prognosis[276,277]
	Gastric	Oncogene	Expression up-regulated[5,278]
	Hepatocellular	Oncogene	Expression up-regulated[4]
TRPM2	Colorectal	Oncogene	Expression up-regulated[270]
	Pancreatic	Oncogene	Expression up-regulated; enhanced proliferation, invasion & metastasis[272,273]
	Gastric	Oncogene	Expression up-regulated; inhibition reduced proliferation of gastric cancer cells, increased autophagy and sensitized cells to paxlitaxel and doxorubicin[68,272,273]
TRPM6	Colorectal	Tumor suppressor	Expression down-regulated in 16/20 (80%) of primary tumors; high expression associated with better patient survival[285]
TRPM7	Colorectal	Not determined	Genetic polymorphism associated with enhanced risk of adenomas, linked to high Ca2+:Mg2+ ratio in diet[268]
	Pancreatic	Oncogene	Expression up-regulated; increased tumor growth, invasiveness and metastasis; targeted silencing induced replicative senescence[5,258-261,263-267]
	Gastric	Oncogene	Highly expressed in gastric cancer cell lines; required for GC survival linked to Mg; suppression induces cell death in culture[4,269-271]
TRPM8	Pancreatic	Oncogene	Expression up-regulated; regulates proliferation and migration; silencing in cell lines induces replicative senescence [259-262]
L-type/a1c subunit/CACNA1C	Colorectal	Oncogene	Expression up-regulated[283]
Sig1R/SIGMAR1	Colorectal	Oncogene	Expression up-regulated in CRC cell lines and primary CRC tumors[280-282]
Stim1/Stromal interaction protein 1	Colorectal	Oncogene	Expression up-regulated; increased CRC cell motility; STIM1 overexpression enhanced lung and liver metastases in mouse xenograft models; also associated with poor prognosis in CRC patients[15,255,256]
	Pancreatic	Oncogene	Expression up-regulated; promotes invasion and metastasis; STIM1 and Orai1 are the molecular components of SOCE[14]
Stim2/Stromal interaction protein 2	Colorectal	Tumor suppressor	Expression down-regulated; depletion causes apoptosis resistance[15,256,274]
Orai1/CRAMC1	Colorectal	Oncogene	Expression up-regulated; activated by STIM1[5]
	Pancreatic	Oncogene	Expression up-regulated; mediate SOCE and promote apoptotic resistance in pancreatic cancer cells[91,279]
	Esophageal	Oncogene	Expression up-regulated; promotes tumor-promoting Ca2+ oscillations in EC[275]
	Gastric	Oncogene	Expression up-regulated; promotes metastasis[68]
T-type CACNA1G/CaV3.1	Colorectal	Tumor suppressor	expression down-regulated by promoter hypermethylation[284,286]
	Pancreatic	Tumor suppressor	Expression down-regulated by promoter hypermethylation[284,287]
	Gastric	Tumor suppressor	Expression down-regulated by promoter hypermethylation; high expression associated with improved overall survival[284,288]
T-type CACNA1I/CaV3.3	Gastric	Oncogene	High expression associated with poor survival[284]
T-type CACNA1H/CaV3.2	Gastric	Oncogene	High expression associated with poor survival[284]
CACNA2D3	Gastric	Tumor suppressor	Expression down-regulated by promoter hypermethylation, associated with worse prognosis[91,289]
CACNB2	Esophageal	Tumor suppressor	Expression down-regulated by promoter hypermethylation[90]

GC: Gastric cancer; CRC: Colorectal cancer; EC: Esophageal cancer; SOCE: Store-operated calcium entry; STIM1: Stromal interaction protein 1.