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

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

Affiliations
  • 1Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea. tgkwon@knu.ac.kr
  • 2Department of Urology, Kyungpook National University Hospital, Daegu, Korea.
  • 3Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, Korea.
  • 4Immunoregulatory 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.

Keyword

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

MeSH Terms

Blotting, Western
Carcinoma, Renal Cell*
Cell Line
Down-Regulation*
Humans
Ion Channels
Neoplasm Invasiveness
Neoplasm Metastasis
Phosphorylation
Protein Kinases
RNA, Small Interfering
Signal Transduction
Wound Healing
Ion Channels
Protein Kinases
RNA, Small Interfering
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