Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cancer

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.

TheHelicobacter pyloritypeIVsecretion system upregulates epithelial cortactin expression by aCagA‐ andJNK‐dependent pathway

“…In our experiments, we identified JNK as an important MAP kinase involved in cortactin overexpression in response to CagA. JNK is a major kinase regulating migration of various human cell types (C. Huang, Rajfur, Borchers, Schaller, & Jacobson, 2003; Z. Huang, Yan, & Ge, 2008; E. H. Lee et al, 2020; Xu & Hu, 2020). Our studies are in agreement with other studies showing that transgenic CagA can induce JNK activation in Drosophila (Wandler & Guillemin, 2012).…”

Prognostic Value of TRPM7 Expression and Factor XIIIa-Expressing Tumor-Associated Macrophages in Gastric Cancer

“…To illustrate, it has been established that Ca 2+ channels play important roles both in the control of cellular growth and proliferation and in the control of cell death [ 25 ]. In recent years, several studies reporting that TRPM7 plays an important role in carcinogenesis and claim that it can be considered as a potential target in the treatment of various cancers have attracted attention [ 9 , 12 ]. As Ca 2+ is an important regulator of cell cycle and proliferation, TRPM7, which is a special member of the TRP channels known to be permeable to Ca 2+ and Mg 2+ , is thought to be highly important in terms of cancer cell biology [ 9 ].…”

“…It is reported that TRPM7 is overexpressed in human pulmonary carcinoma and pancreatic adenocarcinoma [ 29 , 30 ]. In addition, the inhibition and downregulation of TRPM7 by specific chemical agents is known to inhibit the migration and invasion of breast cancer cells, while overexpression has been shown to support the proliferation and migration of lung cancer cells [ 12 , 29 ]. According to Luanpitpong et al, blocking of TRPM7 has repressed cell motility in various non-small-cell lung carcinoma cell lines and patient-derived primary tumor cells.…”

“…According to their results, the 5-year disease-free survival rate in the group with the high density of TAMs was significantly higher than those with the low density [ 38 ]. Contrary, Lu et al found out a negative correlation between TAMs and the prognosis of patients with GC [ 12 ]. They stated that when compared with CD68 + TAM negative patients, DFS rates were significantly lower in CD68 + TAM positive ones [ 14 ].…”

“…These findings implicated that TRPM7 could be a promising molecule for targeted therapies in GC [ 7 ]. In addition to GC, TRPM7 overexpression also has been shown in pancreatic adenocarcinoma, bladder cancer, and breast cancer cells [ 9 , 11 , 12 ]. Studies have determined that upregulation of TRPM7 is necessary for the proliferation of tumor cells.…”