Table 3.
Channels (ion flux) |
Expression in Cancer | Cancer Type | Effects on Wnt Signaling | Mechanism of Action | Effect on Tumorigenesis | Ref. |
---|---|---|---|---|---|---|
Trp5
(non-selective Ca2+ cation channel) |
High | Colorectal cancer | ↑Wnt5a, ↑ Wnt signaling targets (cyclin D1 and c-myc) | ↑ Trp5 increase Ca2+ influx in the cell, which induces ↑Wnt5a and ↑ nuclear β-catenin levels | Channel upregulation reduces colorectal cancer differentiation and stemness through Ca2+-Wnt5a | [59] |
Trp5
(non-selective Ca2+ cation channel) |
High | Colorectal cancer | β-catenin stabilization | Reduction in levels of the channels reduces Ca2+ influx lowering β-catenin stability | Silencing of the channel reduces colorectal cancer tumorigenesis and ameliorates 5-Fluorouracil chemoresistance | [55] |
TRPM4
(non-selective Ca2+ cation channel) |
High | Prostate cancer | ↑β-catenin stabilization | ↑ GSK3β and AKT1 phospho-inactive form through Ca2+ flux | Tumor proliferation and progression | [60] |
TRPV2
(non-selective Ca2+ cation channel) |
High | Esophageal squamous cell carcinoma | ↑ Wnt signaling | Increased Ca2+ flux results in ↑ Wnt signaling. The precise mechanism of action still to be determined. | Promotes proliferation, invasion, and angiogenesis | [61] |
BKCa
(K+) |
High | Breast cancer | ↑β-catenin stabilization | Modulation of transmembrane depolarization regulates phospho-AKT and, in turn, β-catenin stability | Pharmacological inhibition of the channel (Ibtx) reduces anchorage-dependent growth and tumorigenesis | [62] |