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.
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.
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.
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.
BMC urology. 2020 Sep 09*** epublish ***
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
Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea., BioMedical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea., Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea., Department of Urology, Yeungnam University College of Medicine, Daegu, Republic of Korea., Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea. ., Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea. .