Titre :

TRPM8-Rap1A Interaction Sites as Critical Determinants for Adhesion and Migration of Prostate and Other Epithelial Cancer Cells

Auteur(s) :

Chinigo, Giorgia [Auteur]
Università degli studi di Torino = University of Turin [UNITO]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Grolez, Guillaume [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Audero, Madelaine Magalì [Auteur]
Physiologie Cellulaire (PHYCELL) - U1003
Università degli studi di Torino = University of Turin [UNITO]
Bokhobza, Alexandre [Auteur]
Physiologie Cellulaire (PHYCELL) - U1003
Bernardini, Michela [Auteur]
Università degli studi di Torino = University of Turin [UNITO]
Cicero, Julien [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Toillon, Robert [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
Bailleul, Quentin [Auteur]
Physiologie Cellulaire (PHYCELL) - U1003
Visentin, Luca [Auteur]
Università degli studi di Torino = University of Turin [UNITO]
Ruffinatti, Federico Alessandro [Auteur]
Università degli studi di Torino = University of Turin [UNITO]
Brysbaert, Guillaume [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Cantelmo, Anna Rita [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Fiorio Pla, Alessandra [Auteur]
Università degli studi di Torino = University of Turin [UNITO]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Gkika, Dimitra [Auteur]
1004619|||Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
563719|||University of California [Berkeley]
56663|||Institut Universitaire de France [IUF]
Physiologie Cellulaire (PHYCELL) - U1003

Titre de la revue :

Cancers

Numéro :

14

Pagination :

2261

Éditeur :

MDPI

Date de publication :

2022-04-30

ISSN :

2072-6694

Mot(s)-clé(s) en anglais :

GTPase
Rap1A
TRPM8
adhesion
calcium channel
metastasis
migration
prostate cancer

Discipline(s) HAL :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Emerging evidence indicates that the TRPM8 channel plays an important role in prostate cancer (PCa) progression, by impairing the motility of these cancer cells. Here, we reveal a novel facet of PCa motility control via ...
Lire la suite >Emerging evidence indicates that the TRPM8 channel plays an important role in prostate cancer (PCa) progression, by impairing the motility of these cancer cells. Here, we reveal a novel facet of PCa motility control via direct protein-protein interaction (PPI) of the channel with the small GTPase Rap1A. The functional interaction of the two proteins was assessed by active Rap1 pull-down assays and live-cell imaging experiments. Molecular modeling analysis allowed the identification of four putative residues involved in TRPM8-Rap1A interaction. Point mutations of these sites impaired PPI as shown by GST-pull-down, co-immunoprecipitation, and PLA experiments and revealed their key functional role in the adhesion and migration of PC3 prostate cancer cells. More precisely, TRPM8 inhibits cell migration and adhesion by trapping Rap1A in its GDP-bound inactive form, thus preventing its activation at the plasma membrane. In particular, residues E207 and Y240 in the sequence of TRPM8 and Y32 in that of Rap1A are critical for the interaction between the two proteins not only in PC3 cells but also in cervical (HeLa) and breast (MCF-7) cancer cells. This study deepens our knowledge of the mechanism through which TRPM8 would exert a protective role in cancer progression and provides new insights into the possible use of TRPM8 as a new therapeutic target in cancer treatment.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CNRS

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
• Physiologie Cellulaire (PHYCELL) - U1003
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Computational Molecular Systems Biology

Date de dépôt :

2022-11-23T10:38:58Z
2022-11-25T13:16:40Z
2022-11-29T09:45:05Z