Skip to main content

Advertisement

SpringerLink
Log in

Overexpression of integrin-linked kinase (ILK) is associated with tumor progression and an unfavorable prognosis in patients with colorectal cancer

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

Integrin-linked kinase (ILK), an intracellular serine-threonine kinase, has been reported to be overexpressed in multiple types of human malignancies, including colorectal cancer (CRC). The prognostic value of ILK in CRC, however, remains unknown. In the present study, expression of ILK in 25 paired primary CRC samples and adjacent noncancerous tissues were quantified using real-time PCR and Western blotting. ILK protein expression was analyzed in 102 archived, paraffin-embedded CRC samples using immunohistochemistry. The correlation between ILK expression and clinicopathological factors was evaluated by the χ2 test. Patients’ overall survival was analyzed by Kaplan–Meier method. We found that both ILK mRNA and protein expression levels were significantly up-regulated in primary CRC samples compared with their corresponding normal tissues. Immunohistochemical analysis revealed relative high expression of ILK in 43 of 102 (42.2 %) primary CRC samples. Statistical analysis showed a significant correlation of ILK expression with tumor differentiation, lymph node metastasis, tumor invasion, and tumor-node-metastasis stage. Patients with tumors displaying high-level ILK expression showed significantly shorter overall survival (P = 0.028, log-rank test). More importantly, multivariate analysis indicated that high ILK protein expression was an independent prognostic factor for CRC patients (P = 0.026). Taken together, our data suggest that ILK overexpression is associated with tumor progression and a poor prognosis in CRC patients and may represent a novel potential prognostic marker for patients with CRC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Assi K, Mills J, Owen D, Ong C, St Arnaud R, Dedhar S, Salh B (2008) Integrin-linked kinase regulates cell proliferation and tumour growth in murine colitis-associated carcinogenesis. Gut 57(7):931–940. doi:10.1136/gut.2007.142778

    Article  PubMed  CAS  Google Scholar 

  • Bravou V, Klironomos G, Papadaki E, Taraviras S, Varakis J (2006) ILK over-expression in human colon cancer progression correlates with activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway. J Pathol 208(1):91–99. doi:10.1002/path.1860

    Article  PubMed  CAS  Google Scholar 

  • Chan J, Ko FC, Yeung YS, Ng IO, Yam JW (2011) Integrin-linked kinase overexpression and its oncogenic role in promoting tumorigenicity of hepatocellular carcinoma. PLoS ONE 6(2):e16984. doi:10.1371/journal.pone.0016984

    Article  PubMed  CAS  Google Scholar 

  • Chen P, Shen WZ, Karnik P (2004) Suppression of malignant growth of human breast cancer cells by ectopic expression of integrin-linked kinase. Int J Cancer 111(6):881–891. doi:10.1002/ijc.20340

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Zhang Y, Zhang X, Li J, Han B, Liu S, Wang L, Ling Y, Mao S, Wang X (2012) 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. Acta Histochem. doi:10.1016/j.acthis.2012.05.004

    Google Scholar 

  • Dai DL, Makretsov N, Campos EI, Huang C, Zhou Y, Huntsman D, Martinka M, Li G (2003) Increased expression of integrin-linked kinase is correlated with melanoma progression and poor patient survival. Clin Cancer Res 9(12):4409–4414

    PubMed  CAS  Google Scholar 

  • Dedhar S, Williams B, Hannigan G (1999) Integrin-linked kinase (ILK): a regulator of integrin and growth-factor signalling. Trends Cell Biol 9(8):319–323

    Article  PubMed  CAS  Google Scholar 

  • Durbin AD, Hannigan GE, Malkin D (2009) Oncogenic ILK, tumor suppression and all that JNK. Cell Cycle 8(24):4060–4066

    Article  PubMed  CAS  Google Scholar 

  • Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J, Bell JC, Dedhar S (1996) Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature 379(6560):91–96. doi:10.1038/379091a0

    Article  PubMed  CAS  Google Scholar 

  • Hannigan G, Troussard AA, Dedhar S (2005) Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nat Rev Cancer 5(1):51–63. doi:10.1038/nrc1524

    Article  PubMed  CAS  Google Scholar 

  • Hannigan GE, McDonald PC, Walsh MP, Dedhar S (2011) Integrin-linked kinase: not so ‘pseudo’ after all. Oncogene 30(43):4375–4385. doi:10.1038/onc.2011.177

    Article  PubMed  CAS  Google Scholar 

  • Ito R, Oue N, Zhu X, Yoshida K, Nakayama H, Yokozaki H, Yasui W (2003) Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma. Virchows Arch 442(2):118–123. doi:10.1007/s00428-002-0718-6

    PubMed  CAS  Google Scholar 

  • Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59(4):225–249. doi:10.3322/caac.20006

    Article  PubMed  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107

    Article  PubMed  Google Scholar 

  • Li J, Zhang H, Wu J, Guan H, Yuan J, Huang Z, Li M (2010) Prognostic significance of integrin-linked kinase1 overexpression in astrocytoma. Int J Cancer 126(6):1436–1444. doi:10.1002/ijc.24824

    PubMed  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262

    Article  PubMed  CAS  Google Scholar 

  • Marotta A, Tan C, Gray V, Malik S, Gallinger S, Sanghera J, Dupuis B, Owen D, Dedhar S, Salh B (2001) Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis. Oncogene 20(43):6250–6257. doi:10.1038/sj.onc.1204791

    Article  PubMed  CAS  Google Scholar 

  • Marotta A, Parhar K, Owen D, Dedhar S, Salh B (2003) Characterisation of integrin-linked kinase signalling in sporadic human colon cancer. Br J Cancer 88(11):1755–1762. doi:10.1038/sj.bjc.6600939

    Article  PubMed  CAS  Google Scholar 

  • McDonald PC, Fielding AB, Dedhar S (2008) Integrin-linked kinase–essential roles in physiology and cancer biology. J Cell Sci 121(Pt 19):3121–3132. doi:10.1242/jcs.017996

    Article  PubMed  CAS  Google Scholar 

  • O’Connell JB, Maggard MA, Ko CY (2004) Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 96(19):1420–1425. doi:10.1093/jnci/djh275

    Article  PubMed  Google Scholar 

  • Okamura M, Yamaji S, Nagashima Y, Nishikawa M, Yoshimoto N, Kido Y, Iemoto Y, Aoki I, Ishigatsubo Y (2007) Prognostic value of integrin beta1-ILK-pAkt signaling pathway in non-small cell lung cancer. Hum Pathol 38(7):1081–1091. doi:10.1016/j.humpath.2007.01.003

    Article  PubMed  CAS  Google Scholar 

  • Sawai H, Okada Y, Funahashi H, Matsuo Y, Takahashi H, Takeyama H, Manabe T (2006) Integrin-linked kinase activity is associated with interleukin-1 alpha-induced progressive behavior of pancreatic cancer and poor patient survival. Oncogene 25(23):3237–3246. doi:10.1038/sj.onc.1209356

    Article  PubMed  CAS  Google Scholar 

  • Takanami I (2005) Increased expression of integrin-linked kinase is associated with shorter survival in non-small cell lung cancer. BMC Cancer 5:1. doi:10.1186/1471-2407-5-1

    Article  PubMed  Google Scholar 

  • Troussard AA, McDonald PC, Wederell ED, Mawji NM, Filipenko NR, Gelmon KA, Kucab JE, Dunn SE, Emerman JT, Bally MB, Dedhar S (2006) Preferential dependence of breast cancer cells versus normal cells on integrin-linked kinase for protein kinase B/Akt activation and cell survival. Cancer Res 66(1):393–403. doi:10.1158/0008-5472.CAN-05-2304

    Article  PubMed  CAS  Google Scholar 

  • Wani AA, Jafarnejad SM, Zhou J, Li G (2011) Integrin-linked kinase regulates melanoma angiogenesis by activating NF-kappaB/interleukin-6 signaling pathway. Oncogene 30(24):2778–2788. doi:10.1038/onc.2010.644

    Article  PubMed  CAS  Google Scholar 

  • White DE, Cardiff RD, Dedhar S, Muller WJ (2001) Mammary epithelial-specific expression of the integrin-linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice. Oncogene 20(48):7064–7072. doi:10.1038/sj.onc.1204910

    Article  PubMed  CAS  Google Scholar 

  • Wu C, Keightley SY, Leung-Hagesteijn C, Radeva G, Coppolino M, Goicoechea S, McDonald JA, Dedhar S (1998) Integrin-linked protein kinase regulates fibronectin matrix assembly, E-cadherin expression, and tumorigenicity. J Biol Chem 273(1):528–536

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Shi R, Zhang D, Wang E, Qiu X (2011) Expression of integrin-linked kinase in lung squamous cell carcinoma and adenocarcinoma: correlation with E-cadherin expression, tumor microvessel density and clinical outcome. Virchows Arch 458(1):99–107. doi:10.1007/s00428-010-1016-3

    Article  PubMed  CAS  Google Scholar 

  • Zhao G, Guo LL, Xu JY, Yang H, Huang MX, Xiao G (2011) Integrin-linked kinase in gastric cancer cell attachment, invasion and tumor growth. World J Gastroenterol 17(30):3487–3496. doi:10.3748/wjg.v17.i30.3487

    Article  PubMed  CAS  Google Scholar 

  • Zhao D, Tang XF, Yang K, Liu JY, Ma XR (2012) Over-expression of integrin-linked kinase correlates with aberrant expression of Snail, E-cadherin and N-cadherin in oral squamous cell carcinoma: implications in tumor progression and metastasis. Clin Exp Metastasis. doi:10.1007/s10585-012-9485-1

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, Shengjing Hospital, China Medical University, 36 Sanhao Street, Shenyang, 110004, People’s Republic of China

    Rui Li, Baolin Liu, Hongzhuan Yin, Wei Sun, Jianqiao Yin & Qi Su

Authors
  1. Rui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Baolin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hongzhuan Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jianqiao Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qi Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qi Su.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, R., Liu, B., Yin, H. et al. Overexpression of integrin-linked kinase (ILK) is associated with tumor progression and an unfavorable prognosis in patients with colorectal cancer. J Mol Hist 44, 183–189 (2013). https://doi.org/10.1007/s10735-012-9463-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-012-9463-6

Keywords

Search

Navigation