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

Kenji F Shoji1, Elsa Bayet1,2, Sabrina Leverrier-Penna2

  • 1Inserm, EHESP, IRSET, UMR_S 1085, Université de Rennes 1, Rennes, France.

EMBO Reports
|February 6, 2023
PubMed

Insights

The transient receptor potential vanilloid 2 (TRPV2) calcium channel drives melanoma cell migration and invasion. Targeting TRPV2 offers a potential new therapeutic strategy for treating metastatic melanoma.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background:

  • Melanoma is an aggressive skin cancer characterized by rapid metastasis.
  • Aberrant cell motility is a key driver of melanoma invasion and dissemination.
  • Identifying targets to control melanoma cell movement, termed 'migrastatics,' is crucial.

Purpose of the Study:

  • To investigate the role of the TRPV2 calcium channel in melanoma metastasis.
  • To determine if TRPV2 expression and activity are linked to melanoma's aggressive behavior.
  • To explore TRPV2 as a potential therapeutic target and biomarker for metastatic melanoma.

Main Methods:

  • Analysis of TRPV2 expression in melanoma tumors and cell lines.
  • In vitro and in vivo studies assessing cell migration and invasion.
  • TRPV2 silencing experiments in highly metastatic melanoma cells.
  • Localization studies of TRPV2 in invasive melanoma cells.
  • Investigation of downstream signaling pathways involving calcium, calpain, and talin.

Main Results:

  • TRPV2 is prominently expressed in melanoma tumors and linked to metastatic dissemination.
  • TRPV2 activity promotes melanoma cell migration and invasion, while its silencing inhibits these behaviors.
  • TRPV2 localizes to the leading edge of invasive cells, regulating adhesion dynamics and F-actin organization via calcium-calpain-talin signaling.
  • Overexpression of TRPV2 in human melanoma tissues correlates with advanced malignancy and poor prognosis.

Conclusions:

  • The mechanosensitive TRPV2 channel is a key regulator of melanoma cell adhesion and motility.
  • TRPV2 plays a significant role in controlling melanoma cell invasiveness and metastatic potential.
  • TRPV2 represents a promising therapeutic target for migrastatic strategies in metastatic melanoma treatment and a potential biomarker.
Keywords:
TRPV2 channelcalpainmelanomametastasismigration

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