Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cancer
Eun Hye Lee,
So Young Chun,
Bomi Kim,
Bo Hyun Yoon,
Jun Nyung Lee,
Bum Soo Kim,
Eun Sang Yoo,
Sangkyu Lee,
Phil Hyun Song,
Tae Gyun Kwon,
Yun-Sok Ha
Affiliations
Eun Hye Lee
Joint Institute for Regenerative Medicine, Kyungpook National University Hospital
So Young Chun
BioMedical Research Institute, Kyungpook National University Hospital
Bomi Kim
BioMedical Research Institute, Kyungpook National University Hospital
Bo Hyun Yoon
BioMedical Research Institute, Kyungpook National University Hospital
Jun Nyung Lee
Joint Institute for Regenerative Medicine, Kyungpook National University Hospital
Bum Soo Kim
Joint Institute for Regenerative Medicine, Kyungpook National University Hospital
Eun Sang Yoo
Department of Urology, School of Medicine, Kyungpook National University
Sangkyu Lee
BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University
Phil Hyun Song
Department of Urology, Yeungnam University College of Medicine
Tae Gyun Kwon
Joint Institute for Regenerative Medicine, Kyungpook National University Hospital
Yun-Sok Ha
Joint Institute for Regenerative Medicine, Kyungpook National University Hospital
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. 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. 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. 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.
