Transient receptor potential melastatin 4 channel contributes to migration of androgen-insensitive prostate cancer

Christian Holzmann1, Sven Kappel1,2, Tatiana Kilch1,2

  • 1Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Germany.

Oncotarget
|October 27, 2015
PubMed

Insights

Transient Receptor Potential Melastatin 4 (TRPM4) channels elevate sodium influx, reducing calcium entry in prostate cancer. Targeting TRPM4 may offer a new therapeutic strategy for prostate cancer by inhibiting migration.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Impaired calcium (Ca2+) signaling is a hallmark of prostate cancer, promoting proliferation, migration, and resistance to apoptosis.
  • Sodium (Na+) influx through the Transient Receptor Potential Melastatin 4 (TRPM4) channel can decrease Ca2+ influx via store-operated Ca2+ entry (SOCE).
  • TRPM4 gene expression is elevated in prostate cancer patients and identified as a cancer driver in androgen-insensitive prostate cancer.

Purpose of the Study:

  • To investigate TRPM4 protein expression in prostate cancer tissues and cells.
  • To determine the role of TRPM4 in regulating SOCE and cell migration in prostate cancer.

Main Methods:

  • TRPM4 protein levels were assessed in prostate cancer tissue samples and cell lines.
  • TRPM4-mediated Na+ currents were measured in primary human prostate epithelial cells (hPEC) and prostate cancer cell lines (DU145, PC3).
  • Small interfering RNA (siRNA) was used to target TRPM4, and its effects on SOCE, proliferation, and migration were evaluated.

Main Results:

  • Elevated TRPM4 protein levels were observed in prostatic intraepithelial neoplasia (PIN) and prostate cancer tissues compared to healthy tissue.
  • TRPM4 mediated significant Na+ currents in hPEC, DU145, and PC3 cells.
  • TRPM4 knockdown using siRNA significantly increased SOCE in hPEC and DU145 cells.
  • Knockdown of TRPM4 reduced the migration of DU145 and PC3 cells, but did not affect proliferation.

Conclusions:

  • TRPM4 acts as a regulator of SOCE in prostate epithelial cells and prostate cancer cells.
  • TRPM4 plays a role in prostate cancer cell migration.
  • TRPM4 represents a potential therapeutic target for prostate cancer treatment.

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