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Targeting TRPV6/CXCR4 complexes prevents castration-resistant prostate cancer metastasis to the bone

  • 0Laboratory of Cell Physiology, INSERM U1003, Laboratory of Excellence Ion Channels Science and Therapeutics, Equipe Labellisée par la Ligue Nationale Contre le Cancer. Department of Biology, Faculty of Science and Technologies, University of Lille, Villeneuve d'Ascq, France.
Signal Transduction and Targeted Therapy +

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September 4, 2025

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September 4, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

TRPV6 calcium channel expression drives castration-resistant prostate cancer (CRPC) metastasis, particularly to bone. Targeting TRPV6 and CXCR4 together effectively suppresses CRPC spread, offering a new therapeutic strategy.

Area Of Science

  • Oncology
  • Molecular Biology
  • Calcium Channel Research

Background

  • Castration-resistant prostate cancer (CRPC) frequently metastasizes to bone.
  • TRPV6 calcium channel expression is upregulated in prostate cancer and absent in healthy tissue.
  • TRPV6 may facilitate cancer cell adaptation to bone microenvironment and promote metastasis.

Purpose Of The Study

  • To investigate the role of TRPV6 in CRPC aggressiveness and bone metastasis.
  • To elucidate the molecular mechanisms by which TRPV6 promotes invasion and metastasis.
  • To evaluate the therapeutic potential of targeting TRPV6 and CXCR4 in CRPC.

Main Methods

  • Analysis of patient tissue biopsies correlating TRPV6 expression with CRPC aggressiveness and metastasis.
  • In vitro studies on cellular phenotypes, signaling pathways (CaMK2, NF-κB), and marker expression (EMT, MMPs).
  • In vivo studies using trpv6 knockout mice and xenograft models; therapeutic interventions with anti-TRPV6 antibody and CXCR4 inhibitor (AMD3100).

Main Results

  • TRPV6 expression positively correlates with CRPC tumor aggressiveness and metastasis risk.
  • TRPV6 promotes mesenchymal and invasive phenotypes via CaMK2/NF-κB signaling and EMT marker upregulation.
  • TRPV6 forms complexes with CXCR4, enhancing metastasis; dual targeting of TRPV6 and CXCR4 synergistically inhibits metastasis in vivo.

Conclusions

  • TRPV6 is a key driver of CRPC bone metastasis by facilitating cellular invasion and adaptation.
  • The TRPV6/CXCR4 axis represents a critical pathway for CRPC progression.
  • Combined targeting of TRPV6 and CXCR4 demonstrates a promising therapeutic strategy for suppressing CRPC metastasis.