2. Academic Validation
  3. The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential

The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential

  • EMBO Rep. 2023 Feb 6;e55069. doi: 10.15252/embr.202255069.
Kenji F Shoji 1,  Elsa Bayet 1 2,  Sabrina Leverrier-Penna 2,  Dahiana Le Devedec 1,  Aude Mallavialle 3,  Séverine Marionneau-Lambot 4,  Florian Rambow 5 6 7,  Raul Perret 8,  Aurélie Joussaume 1,  Roselyne Viel 9,  Alain Fautrel 9,  Amir Khammari 8,  Bruno Constantin 2,  Sophie Tartare-Deckert 3,  Aubin Penna 1 2
Affiliations

Affiliations

  • 1 Inserm, EHESP, IRSET, UMR_S 1085, Université de Rennes 1, Rennes, France.
  • 2 CNRS, 4CS, Université de Poitiers, Poitiers, France.
  • 3 INSERM, C3M, team 'labellisée Ligue Contre le Cancer 2022, Université Côte d'Azur, Nice, France.
  • 4 Cancéropôle Grand Ouest, In Vivo Platform, Nantes, France.
  • 5 Department of Applied Computational Cancer Research, Institute for AI in Medicine (IKIM), University Hospital Essen, Essen, Germany.
  • 6 University of Duisburg-Essen, Essen, Germany.
  • 7 German Cancer Consortium (DKTK), Partner Site Essen, Essen, Germany.
  • 8 Service de Dermatologie, CHU Nantes, CIC 1413, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes Université, Nantes, France.
  • 9 CNRS, Inserm UMS Biosit, H2P2 Core Facility, Université de Rennes 1, Rennes, France.
PMID: 36744297 DOI: 10.15252/embr.202255069
Abstract

Melanoma is a highly aggressive Cancer endowed with a unique capacity of rapidly metastasizing, which is fundamentally driven by aberrant cell motility behaviors. Discovering "migrastatics" targets, specifically controlling invasion and dissemination of melanoma cells during metastasis, is therefore of primary importance. Here, we uncover the prominent expression of the plasma membrane TRPV2 Calcium Channel as a distinctive feature of melanoma tumors, directly related to melanoma metastatic dissemination. In vitro as well as in vivo, TRPV2 activity is sufficient to confer both migratory and invasive potentials, while conversely TRPV2 silencing in highly metastatic melanoma cells prevents aggressive behavior. In invasive melanoma cells, TRPV2 channel localizes at the leading edge, in dynamic nascent adhesions, and regulates calcium-mediated activation of calpain and the ensuing cleavage of the adhesive protein talin, along with F-actin organization. In human melanoma tissues, TRPV2 overexpression correlates with advanced malignancy and poor prognosis, evoking a biomarker potential. Hence, by regulating adhesion and motility, the mechanosensitive TRPV2 channel controls melanoma cell invasiveness, highlighting a new therapeutic option for migrastatics in the treatment of metastatic melanoma.

Keywords

TRPV2 channel; calpain; melanoma; metastasis; migration.

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