Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression.
Herein we evaluate the involvement of the TRPV2 channel, belonging to the Transient Receptor Potential Vanilloid channel family (TRPVs), in development and progression of different tumor types. In normal cells, the activation of TRPV2 channels by growth factors, hormones, and endocannabinoids induces a translocation of the receptor 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 (e.g., glioblastomas), induces unchecked proliferation, resistance to apoptotic signals and increased resistance to CD95-induced apoptotic cell death. On the other hand, in prostate cancer cells, Ca2+-dependent activation of TRPV2 induced by lysophospholipids increases the invasion of tumor cells. In addition, the progression of prostate cancer to the castration-resistant phenotype is characterized by 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 act as dominant-negative mutant of wild-type TRPV2 channels, by inhibiting its trafficking and translocation to the plasma membrane. In conclusion, as TRP channels are altered in human cancers, and their blockage impair tumor progression, they appear to be a very promising targets for early diagnosis and chemotherapy.
School of Pharmacy, Section of Experimental Medicine, University of Camerino, P.zza dei Costanti, 63032, Camerino, Macerata, Italy. sonia.liberati@uniroma1.it.
Sonia
S
Liberati
School of Pharmacy, Section of Experimental Medicine, University of Camerino, P.zza dei Costanti, 63032, Camerino, Macerata, Italy. beatricemorelli@hotmail.com.
Maria Beatrice
MB
Morelli
School of Pharmacy, Section of Experimental Medicine, University of Camerino, P.zza dei Costanti, 63032, Camerino, Macerata, Italy. consuelo.amantini@unicam.it.
Consuelo
C
Amantini
School of Pharmacy, Section of Experimental Medicine, University of Camerino, P.zza dei Costanti, 63032, Camerino, Macerata, Italy. valerio.farfariello@uniroma1.it.
Valerio
V
Farfariello
Medical Oncology, Polytechnic University of the Marche Region, Via Tronto 10, 60020, Ancona, Italy. mattymo@alice.it.
Matteo
M
Santoni
Medical Oncology, Polytechnic University of the Marche Region, Via Tronto 10, 60020, Ancona, Italy. alessandro.conti@hotmail.com.
Alessandro
A
Conti
School of Pharmacy, Section of Experimental Medicine, University of Camerino, P.zza dei Costanti, 63032, Camerino, Macerata, Italy. massimo.nabissi@unicam.it.
Massimo
M
Nabissi
Medical Oncology, Polytechnic University of the Marche Region, Via Tronto 10, 60020, Ancona, Italy. cascinu@yahoo.com.
Stefano
S
Cascinu
School of Pharmacy, Section of Experimental Medicine, University of Camerino, P.zza dei Costanti, 63032, Camerino, Macerata, Italy. giorgio.santoni@unicam.it.
Giorgio
G
Santoni