Decreased TRPM7 inhibits activities and induces apoptosis of bladder cancer cells via ERK1/2 pathway.
Transient receptor potential melastatin 7 (TRPM7) functions as a Mg2+/Ca2+-permeable channel fused with a kinase domain and regulates various physical processes and diseases. However, its effects on pathogenesis of human bladder cancer (BCa) has not been clarified yet. Our microarray analysis has suggested that calcium signaling pathway is connected with bladder cancer via MAPK pathway. Therefore, we aim to investigate the mechanism of TRPM7 in BCa tumorigenesis by using BCa tissues compared with normal bladder epithelium tissues, as well as using distinct BCa cell lines (EJ, 5637 and T24). We observed increased TRPM7 expression and dysregulation of proteins involved in Epithelial-Mesenchymal Transition (EMT) in BCa tissues. Moreover, knockdown of TRPM7 in BCa cells reversed the EMT status, accompanied by increase of reactive oxygen species (ROS). Furthermore, TRPM7 deficiency could inhibit BCa cell proliferation, migration and invasion, as well as induce p-ERK1/2 and suppress PI3K/AKT at the protein level. Downregulation of TRPM7 promoted cell cycle arrest at G0/G1 phase and apoptosis in vitro, which could be recovered by pre-treatment with U0126 to deactivate ERK1/2, suggesting a close correlation between TRPM7 and the MAPK signaling pathway. Furthermore, a NOD/SCID mouse model transplanted using the BCa cells was established, revealing delayed tumor growth by reduced protein activity and mRNA transcription of TRPM7 in vivo. Our results suggested TRPM7 might be essential for BCa tumorigenesis by interfering BCa cell proliferation, motility and apoptosis.
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Rui
R
Cao
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Zhe
Z
Meng
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Tongzu
T
Liu
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Gang
G
Wang
Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.
Guofeng
G
Qian
Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
Tingting
T
Cao
Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
Xinyuan
X
Guan
Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, MD, USA.
Hancai
H
Dan
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, China.
Yu
Y
Xiao
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Xinghuan
X
Wang
D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015415:Biomarkers; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D064593:Heterografts; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D050053:TRPM Cation Channels / Q000235:genetics*; D059467:Transcriptome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C486583:TRPM7 protein, human
AKT; MAPK; TRPM7; apoptosis; bladder cancer
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