Downregulation of TRPM7 suppressed migration and invasion by regulating epithelial–mesenchymal transition in prostate cancer cells

• Published in: Medical oncology (Northwood, London, England) Vol. 34; no. 7; p. 127
• Main Authors: Chen, Liang, Cao, Rui, Wang, Gang, Yuan, Lushun, Qian, Guofeng, Guo, Zhongqiang, Wu, Chin-Lee, Wang, Xinghuan, Xiao, Yu
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.07.2017; Springer Nature B.V
• Subjects: Cadherins - metabolism; Calcium Signaling; Cell adhesion & migration; Cell Line, Tumor; Cell Movement - genetics; Down-Regulation; Epithelial-Mesenchymal Transition - physiology; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Hematology; Humans; Internal Medicine; Kinases; Male; Medicine; Medicine & Public Health; Metastasis; Oncology; Original Paper; Pathology; Prostate cancer; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - pathology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Tissue Array Analysis; TRPM Cation Channels - genetics; TRPM Cation Channels - metabolism; TRPM7; MMP-2; Prostate cancer; MMP-9; Migration; Invasion
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-017-0987-1

Metastasis is a leading cause of death in patients with prostate cancer (PCa). Transient receptor potential channel 7 (TRPM7) functions as a Mg 2+ /Ca 2+ -permeable channel as well as a protein kinase that regulate various cellular processes including cell adhesion, migration and survival. However, the function of TRPM7 in metastasis of PCa remains largely unknown. Microarray analysis suggested that calcium signaling pathway was significantly altered in metastatic PCa tissues, compared with benign prostatic hyperplasia tissues. Bioinformatics analysis using microarray data and database for annotation, visualization and integrated discovery database revealed altered genes involved in calcium signaling pathway were significantly upregulated in TRPM7 deficiency PCa cells, which was also confirmed by experimental verification. Therefore, we aim to investigate the role of TRPM7 in human PCa cell migration and invasion as well as the underlying mechanisms. We observed that TRPM7 was upregulated in PCa cells and tissues compared with prostate hyperplasia cells and tissues. Further investigations suggested that TRPM7 deficiency suppressed migration and invasion of distinct PCa cell lines while overexpression of TRPM7 increased migration of PCa cells. In addition, knockdown of TRPM7 in PCa cells reversed the epithelial–mesenchymal transition (EMT) status, accompanied by downregulation of MMPs and upregulation of E-cadherin. Taken together, our study indicated that downregulation of TRPM7 could inhibit migration and invasion via reversing EMT status in PCa cells.