NOV is upregulated and promotes migration and invasion in bladder cancer.
NOV is pro-tumourigenic via epithelial-mesenchymal transition (EMT) in several malignancies but is not studied in bladder cancer (BCa). Whether NOV is responsible for bladder carcinogenesis and the underlying mechanism is unclear. Using immunohistochemical staining, we quantified expressions of NOV, pS6, Vimentin and E-cadherin in 66 bladder cancer and 10 normal bladder urothelium samples. EMT was profiled by EMT index (EMTi) calculated as the ratio of Vimentin to E-cadherin. In vitro and in vivo studies were carried out to profile the role of NOV in the tumourigenesis of BCa. NOV was upregulated in bladder cancer compared to normal tissue, and its expression was correlated to pS6 and EMTi. Expression of NOV was higher in recurrent and multiple tumours and was increased with progression of tumour grade. NOV expression was also higher in BCa cell lines. Silence of NOV attenuated EMT, decreased invasion and migration of BCa cells. Silence of NOV also inhibited xenograft tumour growth and decreased tumour EMT. NOV is pro-tumourigenic in bladder cancer especially in nonmuscle-invasive entities (NMIBC). NOV may promote carcinogenesis via promotion of EMT and association with increased mTOR activity.
Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China.
Jie
J
Chen
Yi
Y
Gao
Biyou
B
Xu
Xingang
X
Cui
Danfeng
D
Xu
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D055514:Nephroblastoma Overexpressed Protein / Q000096:biosynthesis* / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
C526319:CCN3 protein, human; D015820:Cadherins; D055514:Nephroblastoma Overexpressed Protein; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases