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TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination
In the fight against prostate cancer (PCa), TRPM8 is one of the most promising clinical targets. Indeed, several studies have highlighted that TRPM8 involvement is key in PCa progression because of its impact on cell proliferation, viability, and migration. However, data from the literature are some...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224463/ https://www.ncbi.nlm.nih.gov/pubmed/35743115 http://dx.doi.org/10.3390/ijms23126672 |
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author | Grolez, Guillaume P. Chinigò, Giorgia Barras, Alexandre Hammadi, Mehdi Noyer, Lucile Kondratska, Kateryna Bulk, Etmar Oullier, Thibauld Marionneau-Lambot, Séverine Le Mée, Marilyne Rétif, Stéphanie Lerondel, Stéphanie Bongiovanni, Antonino Genova, Tullio Roger, Sébastien Boukherroub, Rabah Schwab, Albrecht Fiorio Pla, Alessandra Gkika, Dimitra |
author_facet | Grolez, Guillaume P. Chinigò, Giorgia Barras, Alexandre Hammadi, Mehdi Noyer, Lucile Kondratska, Kateryna Bulk, Etmar Oullier, Thibauld Marionneau-Lambot, Séverine Le Mée, Marilyne Rétif, Stéphanie Lerondel, Stéphanie Bongiovanni, Antonino Genova, Tullio Roger, Sébastien Boukherroub, Rabah Schwab, Albrecht Fiorio Pla, Alessandra Gkika, Dimitra |
author_sort | Grolez, Guillaume P. |
collection | PubMed |
description | In the fight against prostate cancer (PCa), TRPM8 is one of the most promising clinical targets. Indeed, several studies have highlighted that TRPM8 involvement is key in PCa progression because of its impact on cell proliferation, viability, and migration. However, data from the literature are somewhat contradictory regarding the precise role of TRPM8 in prostatic carcinogenesis and are mostly based on in vitro studies. The purpose of this study was to clarify the role played by TRPM8 in PCa progression. We used a prostate orthotopic xenograft mouse model to show that TRPM8 overexpression dramatically limited tumor growth and metastasis dissemination in vivo. Mechanistically, our in vitro data revealed that TRPM8 inhibited tumor growth by affecting the cell proliferation and clonogenic properties of PCa cells. Moreover, TRPM8 impacted metastatic dissemination mainly by impairing cytoskeleton dynamics and focal adhesion formation through the inhibition of the Cdc42, Rac1, ERK, and FAK pathways. Lastly, we proved the in vivo efficiency of a new tool based on lipid nanocapsules containing WS12 in limiting the TRPM8–positive cells’ dissemination at metastatic sites. Our work strongly supports the protective role of TRPM8 on PCa progression, providing new insights into the potential application of TRPM8 as a therapeutic target in PCa treatment. |
format | Online Article Text |
id | pubmed-9224463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92244632022-06-24 TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination Grolez, Guillaume P. Chinigò, Giorgia Barras, Alexandre Hammadi, Mehdi Noyer, Lucile Kondratska, Kateryna Bulk, Etmar Oullier, Thibauld Marionneau-Lambot, Séverine Le Mée, Marilyne Rétif, Stéphanie Lerondel, Stéphanie Bongiovanni, Antonino Genova, Tullio Roger, Sébastien Boukherroub, Rabah Schwab, Albrecht Fiorio Pla, Alessandra Gkika, Dimitra Int J Mol Sci Article In the fight against prostate cancer (PCa), TRPM8 is one of the most promising clinical targets. Indeed, several studies have highlighted that TRPM8 involvement is key in PCa progression because of its impact on cell proliferation, viability, and migration. However, data from the literature are somewhat contradictory regarding the precise role of TRPM8 in prostatic carcinogenesis and are mostly based on in vitro studies. The purpose of this study was to clarify the role played by TRPM8 in PCa progression. We used a prostate orthotopic xenograft mouse model to show that TRPM8 overexpression dramatically limited tumor growth and metastasis dissemination in vivo. Mechanistically, our in vitro data revealed that TRPM8 inhibited tumor growth by affecting the cell proliferation and clonogenic properties of PCa cells. Moreover, TRPM8 impacted metastatic dissemination mainly by impairing cytoskeleton dynamics and focal adhesion formation through the inhibition of the Cdc42, Rac1, ERK, and FAK pathways. Lastly, we proved the in vivo efficiency of a new tool based on lipid nanocapsules containing WS12 in limiting the TRPM8–positive cells’ dissemination at metastatic sites. Our work strongly supports the protective role of TRPM8 on PCa progression, providing new insights into the potential application of TRPM8 as a therapeutic target in PCa treatment. MDPI 2022-06-15 /pmc/articles/PMC9224463/ /pubmed/35743115 http://dx.doi.org/10.3390/ijms23126672 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Grolez, Guillaume P. Chinigò, Giorgia Barras, Alexandre Hammadi, Mehdi Noyer, Lucile Kondratska, Kateryna Bulk, Etmar Oullier, Thibauld Marionneau-Lambot, Séverine Le Mée, Marilyne Rétif, Stéphanie Lerondel, Stéphanie Bongiovanni, Antonino Genova, Tullio Roger, Sébastien Boukherroub, Rabah Schwab, Albrecht Fiorio Pla, Alessandra Gkika, Dimitra TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination |
title | TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination |
title_full | TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination |
title_fullStr | TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination |
title_full_unstemmed | TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination |
title_short | TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination |
title_sort | trpm8 as an anti–tumoral target in prostate cancer growth and metastasis dissemination |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224463/ https://www.ncbi.nlm.nih.gov/pubmed/35743115 http://dx.doi.org/10.3390/ijms23126672 |
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