title: Overexpression of integrin-linked kinase (ILK) promotes migration and invasion of colorectal cancer cells by inducing epithelial-mesenchymal transition via NF-κB signaling.
abstract: Integrin-linked kinase (ILK), a ubiquitously expressed and evolutionally conserved serine/threonine kinase, has been shown to be aberrantly overexpressed and activated in diversified types of human malignancies, including colorectal cancer (CRC). However, the potential role of ILK in cancer cell migration and invasion remains to be elucidated. In this study, we introduced the human ILK gene into a low ILK-expressing human CRC cell line SW480. Cell migration and invasion were evaluated by the wound healing assay and transwell invasion assay, respectively. The epithelial-mesenchymal transition (EMT)-related proteins were detected by Western blot analysis or immunofluorescence. We found that enforced overexpression of ILK in SW480 cells dramatically promoted their migratory and invasive ability in vitro. Furthermore, SW480 cells stably overexpressing ILK underwent EMT, as indicated by mesenchymal morphology, decreased expression of E-cadherin, and increased expression of vimentin, Snail, and Slug. Finally, the nuclear factor (NF)-κB inhibitor BAY 11-7028 or NF-κB p65 small interfering RNA significantly restored the reduced E-cadherin level in ILK-overexpressing cells, suggesting that ILK-mediated down-regulation of E-cadherin is dependent on NF-κB activation. Overall, our study demonstrates a pivotal role of ILK in EMT and metastasis, and suggests novel therapeutic opportunities for the treatment of CRC.
authors.affiliation: Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Zhaopeng
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Intensive Care Unit, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China. Electronic address: cmu2hsuqi@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Su
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099200:Scaffold Protein ILK
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C513384:CDH1 protein, human
keywords: Colorectal cancer; Epithelial–mesenchymal transition; Integrin-linked kinase; Invasion; Migration; Nuclear factor-κB