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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 induce...

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Autores principales: Liberati, Sonia, Morelli, Maria Beatrice, Amantini, Consuelo, Farfariello, Valerio, Santoni, Matteo, Conti, Alessandro, Nabissi, Massimo, Cascinu, Stefano, Santoni, Giorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980744/
https://www.ncbi.nlm.nih.gov/pubmed/24709905
http://dx.doi.org/10.3390/cells3010112
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author Liberati, Sonia
Morelli, Maria Beatrice
Amantini, Consuelo
Farfariello, Valerio
Santoni, Matteo
Conti, Alessandro
Nabissi, Massimo
Cascinu, Stefano
Santoni, Giorgio
author_facet Liberati, Sonia
Morelli, Maria Beatrice
Amantini, Consuelo
Farfariello, Valerio
Santoni, Matteo
Conti, Alessandro
Nabissi, Massimo
Cascinu, Stefano
Santoni, Giorgio
author_sort Liberati, Sonia
collection PubMed
description 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, Ca(2+)-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.
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spelling pubmed-39807442014-04-11 Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression Liberati, Sonia Morelli, Maria Beatrice Amantini, Consuelo Farfariello, Valerio Santoni, Matteo Conti, Alessandro Nabissi, Massimo Cascinu, Stefano Santoni, Giorgio Cells Review 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, Ca(2+)-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. MDPI 2014-02-19 /pmc/articles/PMC3980744/ /pubmed/24709905 http://dx.doi.org/10.3390/cells3010112 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Liberati, Sonia
Morelli, Maria Beatrice
Amantini, Consuelo
Farfariello, Valerio
Santoni, Matteo
Conti, Alessandro
Nabissi, Massimo
Cascinu, Stefano
Santoni, Giorgio
Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression
title Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression
title_full Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression
title_fullStr Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression
title_full_unstemmed Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression
title_short Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression
title_sort loss of trpv2 homeostatic control of cell proliferation drives tumor progression
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980744/
https://www.ncbi.nlm.nih.gov/pubmed/24709905
http://dx.doi.org/10.3390/cells3010112
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