Table 1.
Potassium channels
| Gene name (s) | Cancer | Role | Functional activity |
| KCNA3/Kv1.3 | Colorectal | Unclear | One report that Kv1.3 is frequently hypermethylated and expression down-regulated in CRC; a different report that Kv1.3 is upregulated in human and mouse colon carcinomas[4,76,88] |
| Pancreatic | Tumor suppressor | Expression down-regulated by promoter hypermethylation; promotes metastasis[65,82,89] | |
| KCNA5/Kv1.5 | Gastric | Oncogene | Expression up-regulated; silencing in GC cells inhibits proliferation; alters drug resistance[73,78-80] |
| Colorectal | Oncogene | Expression up-regulated[79] | |
| KCNC1/Kv3.1 | Colorectal | Oncogene | Expression up-regulated[76] |
| KCND1/Kv4.1 | Gastric | Oncogene | Expression up-regulated[81] |
| KCNE2/MiRP1 | Gastric | Tumor suppressor | Expression down-regulated; deficiency promotes tumor progression; knockout mice develop gastritis cystic profundal and neoplasia, pyloric polyadenomas; invasive adenocarcinomas; upregulation of cyclin D1; down-regulated in gastric cancer tissues and cell lines; overexpression in cell lines suppressed growth in soft agar and mouse tumor xenografts[54-58] |
| KCNH1/EAG1/Kv10.1 | Colorectal | Oncogene | Up-regulated; one report showed 75% of CRC tumors positive for Eag1; another report found overexpression in 3.4% of adenocarcinomas[18,75,76] |
| Esophageal | Oncogene | Expression up-regulated; associated with depth of invasion; independent negative prognostic factor[75] | |
| Hepatocellular | Oncogene | Expression up-regulated[16,62,75,77] | |
| KCNH2/hERG1/Kv11.1 | Colorectal | Oncogene | Expression up-regulated; triggers angiogenesis and tumor progression via inducement of PI3K/AKT signaling and HIF1-induced activation of VEGF-A; associated with invasiveness, poor prognosis for stage I and II; up-regulation in ApcMin and AOM mouse models enhanced cancer phenotypes[59-62] |
| Pancreatic | Oncogene | Expression up-regulated in 59% of pancreatic cancers; promotes migration of cancer cells by modulation of f-actin organization; associated with lymph node involvement, tumor grade, TNM stage, poor patient prognosis; linked to EGFR pathway; down-regulated by miR-96; overexpressed in pancreatic cancer cell lines[62-66] | |
| Esophageal | Oncogene | Expression upregulated; promotes progression from Barrett’s esophagus to esophageal cancer; associated with poor patient prognosis[67-70] | |
| Gastric | Oncogene | Expression up-regulated; stimulates angiogenesis by promoting VEGF-A secretion via AKT-dependent regulation of HIF1; positive in 69% of gastric cancers; associated with poor patient prognosis[62,71-74] | |
| KCNH5/EAG2/Kv10.2 | Esophageal | Tumor suppressor | Expression down-regulated by promoter hypermethylation[90] |
| KCNJ3/Kir3.1 | Pancreatic | Oncogene | Expression up-regulated[62,82] |
| KCNN4/Kca3.1 | Colorectal | Oncogene | Expression upregulated; promotes EMT[5,14,83] |
| Pancreatic | Oncogene | Expression up-regulated[65,84] | |
| Hepatocellular | Oncogene | Expression up-regulated[62] | |
| KCNS3/Kv9.3 | Colorectal | Oncogene | Silencing causes inhibition of proliferation of HCT15 CRC cells[85] |
| KCNK9/K2p9.1/Task3 | Colorectal | Oncogene | Expression up-regulated[5,86,87] |
| KCNN3/Kca2.3/SK3 | Colorectal | Oncogene | Expression and activity up-regulated; regulated by SigmaR1; physically coupled to Orai1[5,91] |
| KCNQ1/KvLqt1 | Colorectal | Tumor suppressor | Identified as a top 10 common insertion site (CIS) gene in a sleeping beauty transposon mutagenesis screen in mice; predicted loss of function in the screen; knockout mouse developed enhanced GI cancer phenotype in ApcMin model; expression down-regulated in human colorectal cancer, associated with poor prognosis in stage II, III, and IV disease; found to be down-regulated by β- catenin, which promotes EMT; in turn, KCNQ1 physically interacts with β-catenin, sequestering β-catenin at the plasma membrane[33-38,45] |
| Pancreatic | Not determined | Identified as a common insertion site (CIS) gene in two sleeping beauty transposon mutagenesis screens in mice[39,40] | |
| Gastric | Tumor suppressor | Identified as a CIS gene in a Sleeping Beauty transposon mutagenesis screen; predicted loss of function; knockout mouse susceptible to chronic gastritis, hyperplasia and metaplasia; atrial natriuretic peptide reduced proliferation of gastric cancer cells by upregulating KCNQ1[31,32,42,43] | |
| Hepatocellular | Tumor suppressor | Expression down-regulated by promoter hypermethylation; associated with poor patient prognosis; KCNQ1 regulated EMT; KCNQ1 regulates β-catenin physical interactions at the plasma membrane[41,44] | |
| KCNQ1OT1 | Colorectal | Oncogene | Expression up-regulated; promotes Wnt/β-catenin signaling and migration, poor patient prognosis[49,52] |
| Esophageal | Oncogene | Expression up-regulated; promotion of metastasis; poor patient prognosis[50] | |
| Hepatocellular | Oncogene | Expression up-regulated; competes with endogenous miR-504; promotes cell proliferation, associated with TNM stage and poor survival[51] |
CRC: Colorectal cancer; GC: Gastric cancer; CIS: Common insertion site; EMT: Epithelial to mesenchymal transition; GI: Gastrointestinal.