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Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cancer.
- Source :
-
BMC urology [BMC Urol] 2020 Sep 09; Vol. 20 (1), pp. 145. Date of Electronic Publication: 2020 Sep 09. - Publication Year :
- 2020
-
Abstract
- Background: Bladder cancer (BC) is one of the most common malignancies of the urinary tract. The role of transient receptor potential melastatin 7 (TRPM7) in BC remains unclear. The aim of this study was to investigate the function and signal transduction pathway of TRPM7 in BC.<br />Methods: T24 and UMUC3 cells were used to evaluate the molecular mechanism of TRPM7 by immunoblot analysis. Small interfering RNA was used to knockdown TRPM7, and the effect of silencing TRPM7 was studied by wound healing, migration, and invasion assays in T24 and UMUC3 cells. Xenograft model study was obtained to analyze the effect of TRPM7 inhibition in vivo.<br />Results: Silencing of TRPM7 decreased the migration and invasion ability of T24 and UMUC3 cells. The phosphorylation of Src, Akt, and JNK (c-Jun N-terminal kinase) was also suppressed by TRPM7 silencing. Src, Akt, and JNK inhibitors effectively inhibited the migration and invasion of T24 and UMUC3 cells. In addition, the TRPM7 inhibitor, carvacrol, limited the tumor size in a xenograft model.<br />Conclusion: Our data reveal that TRPM7 regulates the migration and invasion of T24 and UMUC3 cells via the Src, Akt, and JNK signaling pathway. Therefore, TRPM7 suppression could be a potential treatment for BC patients.
- Subjects :
- Animals
Cell Movement
Cell Proliferation
Female
Gene Knockdown Techniques
Humans
Mice
Mice, Inbred BALB C
Neoplasm Invasiveness
Signal Transduction
Tumor Cells, Cultured
Urinary Bladder Neoplasms etiology
MAP Kinase Signaling System physiology
Oncogene Protein pp60(v-src) physiology
Protein Serine-Threonine Kinases genetics
Proto-Oncogene Proteins c-akt physiology
TRPM Cation Channels genetics
Urinary Bladder Neoplasms genetics
Urinary Bladder Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2490
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC urology
- Publication Type :
- Academic Journal
- Accession number :
- 32907556
- Full Text :
- https://doi.org/10.1186/s12894-020-00714-2