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Investig Clin Urol. 2018 Jul;59(4):263-274. doi: 10.4111/icu.2018.59.4.263. Epub 2018 May 18.

Down-regulation of transient receptor potential melastatin member 7 prevents migration and invasion of renal cell carcinoma cells via inactivation of the Src and Akt pathway.

Ha YS1,2, Kim YY3,4, Yu NH1,2, Chun SY1,2, Choi SH1,2, Lee JN1,2, Kim BS1,2, Yoo ES1,2, Kwon TG1,2.

Author information

1
Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea.
2
Department of Urology, Kyungpook National University Hospital, Daegu, Korea.
3
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, Korea.
4
Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Korea.

Abstract

Purpose:

Transient receptor potential melastatin member 7 (TRPM7), an ion channel and serine/threonine protein kinase, has been linked with distinct human malignancies. However, the role of TRPM7 in renal cell carcinoma (RCC) has not been investigated. The aim of this study is to determine whether TRPM7 regulates the migration and invasion of RCC cells. Its relationship with signal transduction pathways was also studied.

Materials and Methods:

The human RCC cell lines ACHN and SN12C were chosen for this study. The molecular mechanisms of TRPM7 action were studied using Western blot analysis and small interfering RNA (siRNA)-based knockdown. The effect of TRPM7 knockdown on RCC cells was measured by using Transwell invasion and wound healing migration assays.

Results:

siRNA-induced silencing of TRPM7 notably decreased the migration and invasion of ACHN and SN12C RCC cells. The phosphorylation levels of Src in both cells were obviously reduced after TRPM7 silencing compared with that of the control ACHN and SN12C cells. Furthermore, the phosphorylation levels of Akt were greatly decreased in ACHN cells after siRNA-induced knockdown of TRPM7. Additionally, the treatment of cells with Src and Akt inhibitors clearly limited the migration and invasion of RCC cells.

Conclusions:

Our data show that TRPM7 regulated ACHN and SN12C RCC cell invasion via the Src/Akt signaling pathway. Therefore, targeting the Src/Akt signaling pathway and/or the expression or function of TRPM7 could be a potential beneficial treatment for patients with RCC.

KEYWORDS:

Carcinoma, renal cell; Neoplasm invasiveness; Neoplasm metastasis; Signal transduction

PMID:
29984342
PMCID:
PMC6028469
DOI:
10.4111/icu.2018.59.4.263
[Indexed for MEDLINE]
Free PMC Article

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