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Published in: Tumor Biology 11/2016

Open Access 01-11-2016 | Original Article

Integrin-linked kinase regulates cadherin switch in bladder cancer

Authors: Dorota Gil, Dorota Ciołczyk-Wierzbicka, Joanna Dulińska-Litewka, Piotr Laidler

Published in: Tumor Biology | Issue 11/2016

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Abstract

Cadherin switch is specific of epithelial-mesenchymal transition (EMT) and is closely related to tumor cell invasion. However, the molecular mechanism that promotes the phenotypic changes remains unclear and elusive. We found that integrin-linked kinase (ILK) is a key factor involved in cadherin switch. The expression and activity of ILK are elevated in a variety of cancers but its mechanisms are not exactly understood. In this report, we studied the role and mechanism of ILK in EMT of human bladder cancer. We showed that silencing of ILK expression by small interfering RNA (siRNA) significantly abolished the nuclear translocation or the presence of markers associated with EMT like Snail, Twist, Zeb, and beta-catenin. ILK knockdown by siRNA suppressed N-cadherin expression and increased re-expression of E-cadherin in bladder cancer cells. We suggest that ILK is a major signaling factor involved in EMT. It is essential to understand the molecular mechanism of EMT in aim to possibly use it in search for new therapeutic targets.
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Literature
1.
go back to reference Ferlay J, Steliavova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403.CrossRefPubMed Ferlay J, Steliavova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403.CrossRefPubMed
2.
go back to reference Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR. Cadherin switching. J Cell Sci. 2008;121:727–35.CrossRefPubMed Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR. Cadherin switching. J Cell Sci. 2008;121:727–35.CrossRefPubMed
3.
go back to reference Gil D, Ciołczyk-Wierzbicka D, Dulińska-Litweka J, Zwawa K, McCubrey JA, Laidler P. The mechanism of contribution of integrin linked kinase (ILK) to epithelial-mesenchymal transition (EMT. Adv Enzym Regul. 2011;51:195–207.CrossRef Gil D, Ciołczyk-Wierzbicka D, Dulińska-Litweka J, Zwawa K, McCubrey JA, Laidler P. The mechanism of contribution of integrin linked kinase (ILK) to epithelial-mesenchymal transition (EMT. Adv Enzym Regul. 2011;51:195–207.CrossRef
4.
go back to reference McDonalds PC, Fielding AB, Dedhar S. Integrin-linked kinase—essential roles in physiology and cancer biology. J Cell Sci. 2008;121:3121–32.CrossRef McDonalds PC, Fielding AB, Dedhar S. Integrin-linked kinase—essential roles in physiology and cancer biology. J Cell Sci. 2008;121:3121–32.CrossRef
5.
go back to reference Oloumi A, McPhee T, Dedhar S. Regulation of E-cadherin expression and β-catenin/Tcf transcriptional activity by the integrin-linked kinase. Biochim Biophys Acta. 2004;1691:1–15.CrossRefPubMed Oloumi A, McPhee T, Dedhar S. Regulation of E-cadherin expression and β-catenin/Tcf transcriptional activity by the integrin-linked kinase. Biochim Biophys Acta. 2004;1691:1–15.CrossRefPubMed
6.
go back to reference Novak A, SC H, Leuhg-Hagesteijn C, et al. Cell adhesion and the integrin-linked kinase regulate the LEF-1 and β-catenin signaling pathways. Proc Natl Acad Sci U S A. 1998;95:4374–9.CrossRefPubMedPubMedCentral Novak A, SC H, Leuhg-Hagesteijn C, et al. Cell adhesion and the integrin-linked kinase regulate the LEF-1 and β-catenin signaling pathways. Proc Natl Acad Sci U S A. 1998;95:4374–9.CrossRefPubMedPubMedCentral
7.
go back to reference Medici D, Nawshad A, Type I. Collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of NF-κB and LEF-1. Matrix Biol. 2009;29:161–5.CrossRefPubMedPubMedCentral Medici D, Nawshad A, Type I. Collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of NF-κB and LEF-1. Matrix Biol. 2009;29:161–5.CrossRefPubMedPubMedCentral
8.
go back to reference Tran C, Costello P, Sanghera J, et al. Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail in APC-/-human colon carcinoma cells. Oncogene. 2001;20:133–40.CrossRef Tran C, Costello P, Sanghera J, et al. Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail in APC-/-human colon carcinoma cells. Oncogene. 2001;20:133–40.CrossRef
9.
go back to reference McPhee TR, McDonald PC, Oloumi A, Dedhar S. Integrin-linked kinase regulates E-cadherin expession through PARP-1. Dev Dynam. 2008;237:2737–47.CrossRef McPhee TR, McDonald PC, Oloumi A, Dedhar S. Integrin-linked kinase regulates E-cadherin expession through PARP-1. Dev Dynam. 2008;237:2737–47.CrossRef
10.
go back to reference Gao J, Zhu J, Li H-Y, Pan H-Y, Jiang R, Chen J-X. Small interfering RNA targeting integrin-linked kinase inhibited the growth and induced apoptosis in human bladder cancer cells. Int J Biochem Cell B. 2011;43:1294–304.CrossRef Gao J, Zhu J, Li H-Y, Pan H-Y, Jiang R, Chen J-X. Small interfering RNA targeting integrin-linked kinase inhibited the growth and induced apoptosis in human bladder cancer cells. Int J Biochem Cell B. 2011;43:1294–304.CrossRef
11.
go back to reference Matsui Y, Assi K, Ogawa O, et al. The importance of integrin-linked kinase in the regulation of bladder cancer invasion. Int J Cancer. 2012;130:521–31.CrossRefPubMed Matsui Y, Assi K, Ogawa O, et al. The importance of integrin-linked kinase in the regulation of bladder cancer invasion. Int J Cancer. 2012;130:521–31.CrossRefPubMed
13.
go back to reference Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H, et al. Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity. J Biol Chem. 2007;282:11221–9.CrossRefPubMedPubMedCentral Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H, et al. Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity. J Biol Chem. 2007;282:11221–9.CrossRefPubMedPubMedCentral
14.
16.
go back to reference Schreiber V, Dantzer F, Ame JG, de Murcia G. Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol. 2006;7:517–28.CrossRefPubMed Schreiber V, Dantzer F, Ame JG, de Murcia G. Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol. 2006;7:517–28.CrossRefPubMed
17.
go back to reference Alexander NR, Tran NL, Rekapally H, Summers CE, Glackin C, Heimark RLN. Cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. Cancer Res. 2006;66:3365–9.CrossRefPubMed Alexander NR, Tran NL, Rekapally H, Summers CE, Glackin C, Heimark RLN. Cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. Cancer Res. 2006;66:3365–9.CrossRefPubMed
18.
go back to reference Shintani Y, Fukumoto Y, Chaika N, Svoboda R, Wheelock MJ, Johnson KR. Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1. J. Cell Biol. 2008;180:1277–89.CrossRefPubMedPubMedCentral Shintani Y, Fukumoto Y, Chaika N, Svoboda R, Wheelock MJ, Johnson KR. Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1. J. Cell Biol. 2008;180:1277–89.CrossRefPubMedPubMedCentral
19.
go back to reference Koenig A, Mueller C, Hasel C, Adler G, Menke A. Collagen type I induces disruption of E-cadherin-mediated cell-cell contacts and promotes proliferation of pancreatic carcinoma cells. Cancer Res. 2006;66:4662–71.CrossRefPubMed Koenig A, Mueller C, Hasel C, Adler G, Menke A. Collagen type I induces disruption of E-cadherin-mediated cell-cell contacts and promotes proliferation of pancreatic carcinoma cells. Cancer Res. 2006;66:4662–71.CrossRefPubMed
20.
go back to reference Kim Y, Kugler MC, Wei Y, et al. Integrin α3β1-dependent β-catenin phosphorylation links epithelial Smad signaling to cell contacts. J. Cell Biol. 2009;184(2):309–22.CrossRefPubMedPubMedCentral Kim Y, Kugler MC, Wei Y, et al. Integrin α3β1-dependent β-catenin phosphorylation links epithelial Smad signaling to cell contacts. J. Cell Biol. 2009;184(2):309–22.CrossRefPubMedPubMedCentral
21.
go back to reference Schaeffer DF, Assi K, Chan K, et al. Tumor expression of integrin-linked kinase (ILK) correlates with the expression of the E-cadherin repressor snail: an immunohistochemical study in ductal pancreatic adenocarcinoma. Virchows Arch. 2010;456:261–8.CrossRefPubMed Schaeffer DF, Assi K, Chan K, et al. Tumor expression of integrin-linked kinase (ILK) correlates with the expression of the E-cadherin repressor snail: an immunohistochemical study in ductal pancreatic adenocarcinoma. Virchows Arch. 2010;456:261–8.CrossRefPubMed
22.
go back to reference McCubrey JA, Davis NM, Abrams SL, et al. Diverse roles of GSK-3: tumor promoter-tumor suppressor, target in cancer therapy. Adv Biol Regulation. 2014;54:176–96.CrossRef McCubrey JA, Davis NM, Abrams SL, et al. Diverse roles of GSK-3: tumor promoter-tumor suppressor, target in cancer therapy. Adv Biol Regulation. 2014;54:176–96.CrossRef
23.
go back to reference Wu C, Dedhar S. Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. J Cell Biol. 2008;155:505–10.CrossRef Wu C, Dedhar S. Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. J Cell Biol. 2008;155:505–10.CrossRef
24.
go back to reference Luo L, Liu H, Dong Z, Sun L, Peng Y, Liu F. Small interfering RNA targeting ILK inhibits EMT in human peritoneal mesothelial cels through phosphorylation of GSK-3β. Mol Med Rep. 2014;10:137–44.PubMed Luo L, Liu H, Dong Z, Sun L, Peng Y, Liu F. Small interfering RNA targeting ILK inhibits EMT in human peritoneal mesothelial cels through phosphorylation of GSK-3β. Mol Med Rep. 2014;10:137–44.PubMed
25.
26.
go back to reference Miyabayashi T, Teo JL, Yamamoto M, McMillan M, Nguyen C, Kahn M. Wnt/β-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency. Proc Natl Acad Sci U S A. 2007;104:5668–73.CrossRefPubMedPubMedCentral Miyabayashi T, Teo JL, Yamamoto M, McMillan M, Nguyen C, Kahn M. Wnt/β-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency. Proc Natl Acad Sci U S A. 2007;104:5668–73.CrossRefPubMedPubMedCentral
27.
go back to reference Yang Z, Zhang X, Gang H, et al. Up-regulation of gastric cancer cell invasion by Twist is accompanied by N-cadherin and fibronectin expression. BBBRC. 2007;925-930. Yang Z, Zhang X, Gang H, et al. Up-regulation of gastric cancer cell invasion by Twist is accompanied by N-cadherin and fibronectin expression. BBBRC. 2007;925-930.
28.
go back to reference Zhou BP, Deng J, Xia W, et al. Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 2004;6:931–40.CrossRefPubMed Zhou BP, Deng J, Xia W, et al. Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 2004;6:931–40.CrossRefPubMed
29.
go back to reference Wu K, Fan J, Zhang L, et al. PI3K/Akt to GSK3β-catenin signaling cascade coordinates cell colonization for bladder cancer bone metastasis through regulating ZEB1 transcription. Cell Signal. 2012;4:2273–82.CrossRef Wu K, Fan J, Zhang L, et al. PI3K/Akt to GSK3β-catenin signaling cascade coordinates cell colonization for bladder cancer bone metastasis through regulating ZEB1 transcription. Cell Signal. 2012;4:2273–82.CrossRef
30.
go back to reference Yang J, Hou Y, Zhou M, Wen S, Zhou J, Xu L, et al. Twist induces epithelial-mesenchymal transition and cell motility in breast cancer via ITGB1-FAK/ILK signaling axis and its associated downstream network. Int J Biochem Cell B. 2016;71:62–71.CrossRef Yang J, Hou Y, Zhou M, Wen S, Zhou J, Xu L, et al. Twist induces epithelial-mesenchymal transition and cell motility in breast cancer via ITGB1-FAK/ILK signaling axis and its associated downstream network. Int J Biochem Cell B. 2016;71:62–71.CrossRef
Metadata
Title
Integrin-linked kinase regulates cadherin switch in bladder cancer
Authors
Dorota Gil
Dorota Ciołczyk-Wierzbicka
Joanna Dulińska-Litewka
Piotr Laidler
Publication date
01-11-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5354-x

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