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

被引：57

作者：

Chen, Donghong ^{[1
]}

Zhang, Yibing ^{[2
]}

Zhang, Xuhua ^{[1
]}

Li, Jing ^{[1
]}

Han, Bing ^{[1
]}

Liu, Shuo ^{[1
]}

Wang, Lingling ^{[1
]}

Ling, Yuan ^{[1
]}

Mao, Shitao ^{[1
]}

Wang, Xiaoge ^{[1
]}

机构：

[1] China Med Univ, Dept Resp Med, Affiliated Hosp 4, Shenyang 110032, Peoples R China

[2] Gen Hosp Shenyang Mil Reg, Dept Resp Med, Shenyang 110016, Peoples R China

来源：

ACTA HISTOCHEMICA | 2013年 / 115卷 / 02期

关键词：

Integrin-linked kinase; Lung cancer; Migration; Invasion; Epithelial-mesenchymal transition; Nuclear factor-kappa B; E-CADHERIN EXPRESSION; PROGNOSTIC-SIGNIFICANCE; KAPPA-B; TRANSCRIPTION; SNAIL; SLUG; ILK; METASTASIS; GROWTH; SUPPRESSION;

D O I：

10.1016/j.acthis.2012.05.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-kappa B (NF-kappa B) inhibitor BAY 11-7028 and small interfering RNA (siRNA) targeting NF-kappa B p65, suggesting a role of the NF-kappa B 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. (C) 2012 Elsevier GmbH. All rights reserved.

引用

页码：128 / 136

页数：9

共 46 条

[11] Oncogenic ILK, tumor suppression and all that JNK [J].

Durbin, Adam David ;

Hannigan, Gregory Edward ;

Malkin, David .

CELL CYCLE, 2009, 8 (24) :4060-4066

[12] The mechanism of contribution of integrin linked kinase (ILK) to epithelial-mesenchymal transition (EMT) [J].

Gil, Dorota ;

Ciolczyk-Wierzbicka, Dorota ;

Dulinka-Litewka, Joanna ;

Zwawa, Karolina ;

McCubrey, James A. ;

Laidler, Piotr .

ADVANCES IN ENZYME REGULATION, VOL 51, 2011, 51 :195-+

[13]

Graff JR, 2001, CLIN CANCER RES, V7, P1987

[14] Enhanced chemosensitivity to irinotecan by RNA interference mediated down-regulation of the nuclear factor-κB p65 subunit [J].

Guo, J ;

Verma, UN ;

Gaynor, RB ;

Frenkel, EP ;

Becerra, CR .

CLINICAL CANCER RESEARCH, 2004, 10 (10) :3333-3341

[15] Regulation of cell adhesion and anchorage-dependent growth by a new beta(1)-integrin-linked protein kinase [J].

Hannigan, GE ;

LeungHagesteijn, C ;

FitzGibbon, L ;

Coppolino, MG ;

Radeva, G ;

Filmus, J ;

Bell, JC ;

Dedhar, S .

NATURE, 1996, 379 (6560) :91-96

[16] NF-κB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression [J].

Huber, MA ;

Azoitei, N ;

Baumann, B ;

Grünert, S ;

Sommer, A ;

Pehamberger, H ;

Kraut, N ;

Beug, H ;

Wirth, T .

JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (04) :569-581

[17] Prognostic significance of hypoxia-inducible factor-1α, TWIST1 and Snail expression in resectable non-small cell lung cancer [J].

Hung, J-J ;

Yang, M-H ;

Hsu, H-S ;

Hsu, W-H ;

Liu, J-S ;

Wu, K-J .

THORAX, 2009, 64 (12) :1082-1089

[18] Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma [J].

Ito, R ;

Oue, N ;

Zhu, XD ;

Yoshida, K ;

Nakayama, H ;

Yokozaki, H ;

Yasui, W .

VIRCHOWS ARCHIV, 2003, 442 (02) :118-123

[19] The basics of epithelial-mesenchymal transition [J].

Kalluri, Raghu ;

Weinberg, Robert A. .

JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (06) :1420-1428

[20] Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world [J].

Kamangar, Farin ;

Dores, Graca M. ;

Anderson, William F. .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (14) :2137-2150

← 1 2 3 4 5 →