2014 Jul 4. [Epub ahead of print]
Advances In Transient Receptor Potential Vanilloid-2 Channel Expression And Function In Tumor Growth And Progression.
Abstract
We evaluate the involvement of TRPV2 channel, belonging to the Transient Receptor Potential Vanilloid channel family (TRPVs), in the progression of different tumor types. In normal cells, the activation of TRPV2 by growth factors, hormones and endocannabinoids induces its translocation from the endosomal compartment to the plasma membrane, which results in abrogation of cell proliferation and induction of cell death. Consequently, loss or inactivation of TRPV2 signaling induces unchecked proliferation, resistance to apoptotic signals. On the other hand, in prostate cancer cells, Ca2+-dependent activation of TRPV2 induced by lysophospholipids and adrenomedullin, increases migration and invasion of tumor cells. The progression of prostate cancer to the castration-resistant phenotype requires de novo TRPV2 expression, with higher TRPV2 transcript levels in patients with metastatic cancer. Finally, TRPV2 functional expression in tumor cells can also depend on the presence of alternative splice variants of TRPV2 mRNA that acts as dominant negative mutant of wild-type TRPV2 channels, by inhibiting its trafficking and translocation to the plasma membrane. Thus, in bladder cancer tumors, loss or reduction of a short TRPV2 variant during cancer progression is associated with the acquisition of an invasive phenotype and a malignant behaviour. High expression of TRPV2 was observed more frequently in esophageal squamous cell carcinoma patients with advanced pT stage, lymph node metastasis and advanced pathological stage. In conclusion, as TRP channels are altered in human cancer, and their blockade impairs the neoplastic progression, they appear to be a very promising target for tumor diagnosis and therapy.
- PMID:
25001513
[PubMed – as supplied by publisher]
