Transient receptor potential melastatin 4 channel contributes to migration of androgen-insensitive prostate cancer cells.
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.
Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Germany.
Christian
C
Holzmann
Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Germany.|Center of Human and Molecular Biology, Saarland University, Homburg, Germany.
Sven
S
Kappel
Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Germany.|Center of Human and Molecular Biology, Saarland University, Homburg, Germany.
Tatiana
T
Kilch
Center of Human and Molecular Biology, Saarland University, Homburg, Germany.|Clinics of Urology and Pediatric Urology, Saarland University, Homburg, Germany.
Marcus Martin
MM
Jochum
Center of Human and Molecular Biology, Saarland University, Homburg, Germany.|Department of Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
Sabine Katharina
SK
Urban
Clinics of Urology and Pediatric Urology, Saarland University, Homburg, Germany.
Volker
V
Jung
Clinics of Urology and Pediatric Urology, Saarland University, Homburg, Germany.
Michael
M
Stöckle
Center of Human and Molecular Biology, Saarland University, Homburg, Germany.|Department of Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
Karen
K
Rother
Center of Human and Molecular Biology, Saarland University, Homburg, Germany.|Department of Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
Markus
M
Greiner
Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Germany.|Center of Human and Molecular Biology, Saarland University, Homburg, Germany.
Christine
C
Peinelt
D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D009361:Neoplasm Invasiveness; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D012964:Sodium / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D012964:Sodium
Ca2+ signaling; cancer driver gene; cell migration; prostate cancer; transient receptor potential melastatin 4 channel (TRPM4)