Overexpression of integrin-linked kinase correlates with malignant phenotype in non-small cell lung cancer and promotes lung cancer cell invasion and migration via regulating epithelial-mesenchymal transition (EMT)-related genes.
Integrin-linked kinase (ILK), a member of the serine/threonine kinases, has been implicated in oncogenesis and progression of human cancers. The aim of this study was to characterize the role of ILK in lung cancer aggressiveness and the underlying molecular mechanisms. ILK protein expression was assessed by immunohistochemistry in a cohort of non-small cell lung cancer (NSCLC) patients, and a series of in vitro assays was conducted to elucidate the function of ILK in lung cancer. Overexpression of ILK protein was detected in 30.6% (33/108) of primary NSCLC tissues and correlated with the TNM stage (P=0.001) and lymph node metastasis (P=0.033). Ectopic overexpression of ILK in lung cancer cells promoted cell migration and invasion in vitro, and led to the acquisition of epithelial-mesenchymal transition (EMT) phenotype, as evidenced by the spindle-like morphology, down-regulation of E-cadherin, and up-regulation of vimentin, fibronectin, Snail and Slug. In addition, the down-regulation of E-cadherin induced by ILK was significantly reversed by nuclear factor-κB (NF-κB) inhibitor BAY 11-7028 and small interfering RNA (siRNA) targeting NF-κB p65, suggesting a role of the NF-κB signaling pathway in ILK-induced EMT. Overall, our results suggest that ILK promotes lung cancer cell migration and invasion through the induction of EMT process.
Department of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, People's Republic of China.
Donghong
D
Chen
Yibing
Y
Zhang
Xuhua
X
Zhang
Jing
J
Li
Bing
B
Han
Shuo
S
Liu
Lingling
L
Wang
Yuan
Y
Ling
Shitao
S
Mao
Xiaoge
X
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008175:Lung Neoplasms / Q000201:enzymology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry; D014945:Wound Healing; D000099200:Scaffold Protein ILK
D003094:Collagen; D004338:Drug Combinations; D007797:Laminin; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans; D000099200:Scaffold Protein ILK; C059485:matrigel