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

Holzmann, Christian; Kappel, Sven; Kilch, Tatiana; Jochum, Marcus Martin; Urban, Sabine Katharina; Jung, Volker; Stöckle, Michael; Rother, Karen; Greiner, Markus; Peinelt, Christine (2015). Transient receptor potential melastatin 4 channel contributes to migration of androgen-insensitive prostate cancer cells. OncoTarget, 6(39), pp. 41783-41793. Impact Journals LLC 10.18632/oncotarget.6157

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Kappel, Sven and Peinelt, Christine

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Christine Peinelt

Date Deposited:

18 Jun 2018 12:22

Last Modified:

18 Jun 2018 12:22

Publisher DOI:

10.18632/oncotarget.6157

PubMed ID:

26496025

Uncontrolled Keywords:

Ca2+ signaling cancer driver gene cell migration prostate cancer transient receptor potential melastatin 4 channel (TRPM4)

BORIS DOI:

10.7892/boris.97448

URI:

https://boris.unibe.ch/id/eprint/97448

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