Integrin-linked kinase regulates cadherin switch in bladder cancer.
Cadherin switch is specific of epithelial-mesenchymal transition (EMT) and is closely related to tumor cell invasion. However, the molecular mechanism that promotes the phenotypic changes remains unclear and elusive. We found that integrin-linked kinase (ILK) is a key factor involved in cadherin switch. The expression and activity of ILK are elevated in a variety of cancers but its mechanisms are not exactly understood. In this report, we studied the role and mechanism of ILK in EMT of human bladder cancer. We showed that silencing of ILK expression by small interfering RNA (siRNA) significantly abolished the nuclear translocation or the presence of markers associated with EMT like Snail, Twist, Zeb, and beta-catenin. ILK knockdown by siRNA suppressed N-cadherin expression and increased re-expression of E-cadherin in bladder cancer cells. We suggest that ILK is a major signaling factor involved in EMT. It is essential to understand the molecular mechanism of EMT in aim to possibly use it in search for new therapeutic targets.
Chair of Medical Biochemistry, Jagiellonian University Medical College, ul.Kopernika 7, 31-034, Kraków, Poland. dorotabeata.gil@uj.edu.pl.
Dorota
http://orcid.org/0000-0002-2318-7360
D
Gil
Chair of Medical Biochemistry, Jagiellonian University Medical College, ul.Kopernika 7, 31-034, Kraków, Poland.
Dorota
D
Ciołczyk-Wierzbicka
Chair of Medical Biochemistry, Jagiellonian University Medical College, ul.Kopernika 7, 31-034, Kraków, Poland.
Joanna
J
Dulińska-Litewka
Chair of Medical Biochemistry, Jagiellonian University Medical College, ul.Kopernika 7, 31-034, Kraków, Poland.
Piotr
P
Laidler
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000099200:Scaffold Protein ILK
D015703:Antigens, CD; D015820:Cadherins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK; C050361:CDH2 protein, human
Cadherin; EMT; ILK; Snail; Twist; Zeb
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