In vitro and in vivo effects of short hairpin RNA targeting integrin-linked kinase in prostate cancer cells

Yuan,Yeqing; Xiao,Yunbei; Li,Qing; Liu,Zhenhua; Zhang,Xiaowei; Qin,Caipeng; Xie,Jing; Wang,Xiaofeng; Xu,Tao

doi:10.3892/mmr.2013.1532

In vitro and in vivo effects of short hairpin RNA targeting integrin-linked kinase in prostate cancer cells

Authors:
- Yeqing Yuan
- Yunbei Xiao
- Qing Li
- Zhenhua Liu
- Xiaowei Zhang
- Caipeng Qin
- Jing Xie
- Xiaofeng Wang
- Tao Xu
View Affiliations

Affiliations: Department of Urology, Peking University People's Hospital, Beijing 100044, P.R. China, Department of Urology, Wenzhou People's Hospital, Wenzhou 325000, P.R. China
Published online on: June 19, 2013 https://doi.org/10.3892/mmr.2013.1532
Pages: 419-424

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Integrin-linked kinase (ILK) localizes at focal adhesion sites, plays an important role in cell-matrix interactions and is involved in the regulation of tumor cell growth and migration. The aim of the present study was to clarify the functional characterization of ILK in prostate cancer (PCa) cells. ILK was shown to be overexpressed in 57.1% (36/63) of PCa samples and 18.2% (2/11) of benign prostatic hyperplasia (BPH) samples using immunohistochemical analysis. DU145 PCa cells knocked down for ILK were examined using western blot analysis, proliferation assay, flow cytometry and wound healing assay. Depletion of ILK significantly impaired cell growth and motility, induced apoptosis in vitro, and delayed xenograft tumor proliferation in nude mice, which were important for oncogenesis and tumor progression. Western blot analysis showed that Akt activity was attenuated in ILK‑depleted cells compared with the control cells. These results indicate that ILK knockdown attenuates the biological behavior of PCa cells by decreasing Akt activity, demonstrating that ILK is involved in the development and progression of PCa. Thus, ILK is suggested to serve as a potential therapeutic target for PCa.

View Figures

View References

1	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar
2	Loblaw DA, Mendelson DS, Talcott JA, et al: American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. J Clin Oncol. 22:2927–2941. 2004. View Article : Google Scholar
3	Feldman BJ and Feldman D: The development of androgen-independent prostate cancer. Nat Rev Cancer. 1:34–45. 2001. View Article : Google Scholar : PubMed/NCBI
4	Hannigan GE, Bayani J, Weksberg R, et al: Mapping of the gene encoding the integrin-linked kinase, ILK, to human chromosome 11p15.5-p15.4. Genomics. 42:177–179. 1997. View Article : Google Scholar : PubMed/NCBI
5	Hannigan G, Troussard AA and Dedhar S: Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nat Rev Cancer. 5:51–63. 2005. View Article : Google Scholar : PubMed/NCBI
6	Gil D, Ciolczyk-Wierzbicka D, Dulinska-Litewka J, Zwawa K, McCubrey JA and Laidler P: The mechanism of contribution of integrin linked kinase (ILK) to epithelial-mesenchymal transition (EMT). Adv Enzyme Regul. 51:195–207. 2011. View Article : Google Scholar : PubMed/NCBI
7	Gao J, Zhu J, Li HY, Pan XY, Jiang R and Chen JX: Small interfering RNA targeting integrin-linked kinase inhibited the growth and induced apoptosis in human bladder cancer cells. Int J Biochem Cell Biol. 43:1294–1304. 2011. View Article : Google Scholar : PubMed/NCBI
8	Ahmed N, Riley C, Oliva K, Stutt E, Rice GE and Quinn MA: Integrin-linked kinase expression increases with ovarian tumour grade and is sustained by peritoneal tumour fluid. J Pathol. 201:229–237. 2003. View Article : Google Scholar : PubMed/NCBI
9	Bravou V, Klironomos G, Papadaki E, Taraviras S and Varakis J: 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. 208:91–99. 2006. View Article : Google Scholar : PubMed/NCBI
10	Intaraprasong P, Assi K, Owen DA, et al: Expression of integrin-linked kinase is not a useful prognostic marker in resected hepatocellular cancer. Anticancer Res. 27:4371–4376. 2007.PubMed/NCBI
11	Goulioumis AK, Bravou V, Varakis J, Goumas P and Papadaki H: Integrin-linked kinase cytoplasmic and nuclear expression in laryngeal carcinomas. Virchows Arch. 453:511–519. 2008. View Article : Google Scholar : PubMed/NCBI
12	Muranyi AL, Dedhar S and Hogge DE: Targeting integrin linked kinase and FMS-like tyrosine kinase-3 is cytotoxic to acute myeloid leukemia stem cells but spares normal progenitors. Leuk Res. 34:1358–1365. 2010. View Article : Google Scholar
13	Wong RP, Ng P, Dedhar S and Li G: The role of integrin-linked kinase in melanoma cell migration, invasion, and tumor growth. Mol Cancer Ther. 6:1692–1700. 2007. View Article : Google Scholar : PubMed/NCBI
14	Graff JR, Deddens JA, Konicek BW, et al: Integrin-linked kinase expression increases with prostate tumor grade. Clin Cancer Res. 7:1987–1991. 2001.PubMed/NCBI
15	Sasaki T, Ryo A, Uemura H, et al: An immunohistochemical scoring system of prolyl isomerase Pin1 for predicting relapse of prostate carcinoma after radical prostatectomy. Pathol Res Pract. 202:357–364. 2006. View Article : Google Scholar : PubMed/NCBI
16	Hou Y, Mortimer L and Chadee K: Entamoeba histolytica cysteine proteinase 5 binds integrin on colonic cells and stimulates NFkappaB-mediated pro-inflammatory responses. J Biol Chem. 285:35497–35504. 2010. View Article : Google Scholar : PubMed/NCBI
17	Buchheit CL, Rayavarapu RR and Schafer ZT: The regulation of cancer cell death and metabolism by extracellular matrix attachment. Semin Cell Dev Biol. 23:402–411. 2012. View Article : Google Scholar : PubMed/NCBI
18	Lu P, Takai K, Weaver VM and Werb Z: Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol. 3:a0050582011.PubMed/NCBI
19	Delcommenne M, Tan C, Gray V, Rue L, Woodgett J and Dedhar S: Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc Natl Acad Sci USA. 95:11211–11216. 1998. View Article : Google Scholar : PubMed/NCBI
20	Persad S, Attwell S, Gray V, et al: Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells. Proc Natl Acad Sci USA. 97:3207–3212. 2000. View Article : Google Scholar : PubMed/NCBI
21	Troussard AA, McDonald PC, Wederell ED, et al: Preferential dependence of breast cancer cells versus normal cells on integrin-linked kinase for protein kinase B/Akt activation and cell survival. Cancer Res. 66:393–403. 2006. View Article : Google Scholar : PubMed/NCBI
22	Hers I, Vincent EE and Tavare JM: Akt signalling in health and disease. Cell Signal. 23:1515–1527. 2011. View Article : Google Scholar : PubMed/NCBI