Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784733369309855744
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
work_keys_str_mv AT grolezguillaumep trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT chinigogiorgia trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT barrasalexandre trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT hammadimehdi trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT noyerlucile trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT kondratskakateryna trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT bulketmar trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT oullierthibauld trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT marionneaulambotseverine trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT lemeemarilyne trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT retifstephanie trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT lerondelstephanie trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT bongiovanniantonino trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT genovatullio trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT rogersebastien trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT boukherroubrabah trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT schwabalbrecht trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT fiorioplaalessandra trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination
AT gkikadimitra trpm8asanantitumoraltargetinprostatecancergrowthandmetastasisdissemination