title: A new PKCα/β/TBX3/E-cadherin pathway is involved in PLCε-regulated invasion and migration in human bladder cancer cells.
abstract: Although PLCε has been verified to enhance bladder cancer cell invasion, the signaling pathways responsible for this remain elusive. Protein kinase C (PKCα/β), which is involved in cancer development and progression, has been demonstrated to be activated by PLCε. However, the roles of PKCα/β in PLCε-mediated bladder carcinoma cell invasion and migration have not been clearly identified. In this study, to determine what role PKCα/β plays in PLCε-mediated bladder cancer cell invasion and migration, we silenced PLCε gene by adenovirus-shPLCε in T24 and BIU-87 cells and then revealed that it significantly inhibited cell migration and invasion. Further research indicated that cell bio-function of PLCε-regulated was related with PKCα/β activity. These in vitro findings were supported by data from bladder carcinoma patient samples. In 35 case bladder cancer tumor samples, PLCε-overexpressing tumors showed significantly higher positive rates of PKCα/β membrane immunohistochemistry staining than PLCε-low-expressing tumors. Mechanistically, study further showed that PLCε knockdown gene induced E-cadherin expression and decreased TBX3 expression, both of which were dependent on PKCα/β activity. In addition, we demonstrated that treatment cells with TBX3-specific shorting hairpin RNA (shRNA) up-regulated E-cadherin expression and inhibited cell invasion/migration. Moreover, in in vivo experiment, immunohistochemistry analysis of Ad-shPLCε-infected tumor tissue showed low expression levels of phospho-PKCα/β and TBX3 and high expression levels of E-cadherin compared with those of the control group. In summary, our findings uncover that PKCα/β is critical for PLCε-mediated cancer cell invasion and migration and provide valuable insights for current and future Ad-shPLCε and PKCα/β clinical trials.
authors: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Hong Fei
authors: HF
authors: Du
authors: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Li Ping
authors: LP
authors: Ou
authors: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Xue
authors: X
authors: Yang
authors: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Xue Dong
authors: XD
authors: Song
authors: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Yan Ru
authors: YR
authors: Fan
authors: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors: Bing
authors: B
authors: Tan
authors: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, People's Republic of China. Electronic address: luochunli79@126.com.
authors: Chun Li
authors: CL
authors: Luo
authors: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors: Xiao Hou
authors: XH
authors: Wu
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009368:Neoplasm Transplantation; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D015820:Cadherins; D002227:Carbazoles; D034741:RNA, Small Interfering; D020825:T-Box Domain Proteins; C106884:TBX3 protein, human; C081021:Go 6976; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon
keywords: Bladder cancer; E-cadherin; Invasion; Migration; PKCα; PKCα/β; PKCβ; PLCε; Phospholipase Cε; TBX3; protein kinase Cα; protein kinase Cβ