Related Experiment Video
Updated: Mar 31, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
Published on: May 19, 2016
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.
Abstract:
Impaired Ca2+ signaling in prostate cancer contributes to several cancer hallmarks, such as enhanced proliferation and migration and a decreased ability to induce apoptosis. Na+ influx via transient receptor potential melastatin 4 channel (TRPM4) can reduce store-operated Ca2+ entry (SOCE) by decreasing the driving force for Ca2+. In patients with prostate cancer, gene expression of TRPM4 is elevated. Recently, TRPM4 was identified as a cancer driver gene in androgen-insensitive prostate cancer.We investigated TRPM4 protein expression in cancer tissue samples from 20 patients with prostate cancer. We found elevated TRPM4 protein levels in prostatic intraepithelial neoplasia (PIN) and prostate cancer tissue compared to healthy tissue. In primary human prostate epithelial cells (hPEC) from healthy tissue and in the androgen-insensitive prostate cancer cell lines DU145 and PC3, TRPM4 mediated large Na+ currents. We demonstrated significantly increased SOCE after siRNA targeting of TRPM4 in hPEC and DU145 cells. In addition, knockdown of TRPM4 reduced migration but not proliferation of DU145 and PC3 cells. Taken together, our data identify TRPM4 as a regulator of SOCE in hPEC and DU145 cells, demonstrate a role for TRPM4 in cancer cell migration and suggest that TRPM4 is a promising potential therapeutic target.
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.
Related Concept Videos
Chemotaxis and Direction of Cell Migration
Cancer Cell Migration through Invadopodia
Cell Polarization by Rho Proteins
Cell Migration
Thermosensation

