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Published in: Tumor Biology 4/2014

01-04-2014 | Research Article

Filamin A regulates MMP-9 expression and suppresses prostate cancer cell migration and invasion

Authors: G. G. Sun, Y. F. Lu, J. Zhang, W. N. Hu

Published in: Tumor Biology | Issue 4/2014

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Abstract

This study aims to analyze the expression and clinical significance of Filamin A (FLNA) in prostate carcinoma and the biological effect in its cell line by FLNA overexpression. Immunohistochemistry and Western blot were used to analyze FLNA protein expression in 68 cases of prostate cancer and 37 cases of normal tissues to study the influence of the upregulated expression of FLNA that might be found on PC-3 cell biological effect. In the immunohistochemical analysis, the level of FLNA protein expression was found to be significantly lower in prostate cancer tissue than in normal tissues (P < 0.05). In the Western blot analysis, the relative amount of FLNA protein in prostate cancer tissue was found to be significantly lower than in normal tissues (P < 0.05). The level of FLNA protein expression was not correlated with age and PSA concentration (P > 0.05), but it was correlated with T stages, lymph node metastasis, clinic stage, and Gleason score (P < 0.05). The result of biological function showed that PC-3 cell transfected FLNA had a lower survival fraction, a significant decrease in migration and invasion, and a lower matrix metallopeptidase 9 (MMP-9) protein expression compared with PC-3 cell untransfected FLNA (P < 0.05). FLNA expression decreased in prostate cancer and correlated significantly with T stages, lymph node metastasis, clinic stage, and Gleason score, suggesting that FLNA may play important roles as a negative regulator to prostate cancer PC-3 cell by promoting the degradation of MMP-9.
Literature
1.
go back to reference Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000;50:7–33.PubMedCrossRef Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000;50:7–33.PubMedCrossRef
2.
go back to reference Dong JT, Isaacs WB, Isaacs JT. Molecular advances in prostate cancer. Curr Opin Oncol. 1997;9:101–7.PubMedCrossRef Dong JT, Isaacs WB, Isaacs JT. Molecular advances in prostate cancer. Curr Opin Oncol. 1997;9:101–7.PubMedCrossRef
3.
go back to reference Zhou X, Boren J, Akyurek LM. Filamins in cardiovascular development. Trends Cardiovasc Med. 2007;17:222–9.PubMedCrossRef Zhou X, Boren J, Akyurek LM. Filamins in cardiovascular development. Trends Cardiovasc Med. 2007;17:222–9.PubMedCrossRef
4.
go back to reference Ai J, Huang H, Lv X, Tang Z, Chen M, Chen T, et al. FLNA and PGK1 are two potential markers for progression in hepatocellular carcinoma. Cell Physiol Biochem. 2011;27:207–16.PubMedCrossRef Ai J, Huang H, Lv X, Tang Z, Chen M, Chen T, et al. FLNA and PGK1 are two potential markers for progression in hepatocellular carcinoma. Cell Physiol Biochem. 2011;27:207–16.PubMedCrossRef
5.
go back to reference Stossel TP, Condeelis J, Cooley L, Hartwig JH, Noegel A, Schleicher M, et al. Filamins as integrators of cell mechanics and signalling. Nat Rev Mol Cell Biol. 2001;2:138–45.PubMedCrossRef Stossel TP, Condeelis J, Cooley L, Hartwig JH, Noegel A, Schleicher M, et al. Filamins as integrators of cell mechanics and signalling. Nat Rev Mol Cell Biol. 2001;2:138–45.PubMedCrossRef
6.
go back to reference Sheen VL, Feng Y, Graham D, Takafuta T, Shapiro SS, Walsh CA. Filamin A and Filamin B are co-expressed within neurons during periods of neuronal migration and can physically interact. Hum Mol Genet. 2002;11:2845–54.PubMedCrossRef Sheen VL, Feng Y, Graham D, Takafuta T, Shapiro SS, Walsh CA. Filamin A and Filamin B are co-expressed within neurons during periods of neuronal migration and can physically interact. Hum Mol Genet. 2002;11:2845–54.PubMedCrossRef
7.
go back to reference Feng Y, Walsh CA. The many faces of filamin: a versatile molecular scaffold for cell motility and signalling. Nat Cell Biol. 2004;6:1034–8.PubMedCrossRef Feng Y, Walsh CA. The many faces of filamin: a versatile molecular scaffold for cell motility and signalling. Nat Cell Biol. 2004;6:1034–8.PubMedCrossRef
8.
go back to reference Bedolla RG, Wang Y, Asuncion A, Chamie K, Siddiqui S, Mudryj MM, et al. Nuclear versus cytoplasmic localization of filamin A in prostate cancer: immunohistochemical correlation with metastases. Clin Cancer Res. 2009;15:788–96.PubMedCentralPubMedCrossRef Bedolla RG, Wang Y, Asuncion A, Chamie K, Siddiqui S, Mudryj MM, et al. Nuclear versus cytoplasmic localization of filamin A in prostate cancer: immunohistochemical correlation with metastases. Clin Cancer Res. 2009;15:788–96.PubMedCentralPubMedCrossRef
9.
go back to reference Bourguignon LY, Gilad E, Peyrollier K. Heregulin-mediated ErbB2-ERK signaling activates hyaluronan synthases leading to CD44-dependent ovarian tumor cell growth and migration. J Biol Chem. 2007;282:19426–41.PubMedCrossRef Bourguignon LY, Gilad E, Peyrollier K. Heregulin-mediated ErbB2-ERK signaling activates hyaluronan synthases leading to CD44-dependent ovarian tumor cell growth and migration. J Biol Chem. 2007;282:19426–41.PubMedCrossRef
10.
go back to reference Feng YY, Walsh CA. The many faces of flamin: a versatile molecular scaffold for cell motility and signaling. Nat Cell Biol. 2004;6:1034–8.PubMedCrossRef Feng YY, Walsh CA. The many faces of flamin: a versatile molecular scaffold for cell motility and signaling. Nat Cell Biol. 2004;6:1034–8.PubMedCrossRef
12.
go back to reference Roberson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, et al. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet. 2003;33:487–91.CrossRef Roberson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, et al. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet. 2003;33:487–91.CrossRef
13.
go back to reference Keshamouni VG, Michailidis G, Grasso CS, Anthwal S, Strahler JR, Walker A, et al. Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype. J Proteome Res. 2006;5:1143–54.PubMedCrossRef Keshamouni VG, Michailidis G, Grasso CS, Anthwal S, Strahler JR, Walker A, et al. Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype. J Proteome Res. 2006;5:1143–54.PubMedCrossRef
14.
go back to reference Shi JW, Yu YM, Wang SJ, Zhang J, Wang GY. Expressions of filamin A and matrix metalloproteinase 9 in colorectal adenocarcinoma and their significance. Tumor. 2010;30:768–73. Shi JW, Yu YM, Wang SJ, Zhang J, Wang GY. Expressions of filamin A and matrix metalloproteinase 9 in colorectal adenocarcinoma and their significance. Tumor. 2010;30:768–73.
15.
go back to reference Wu YP, Li JB, Zhao RJ, Zhao RJ, Wang XL, Shan BE, et al. Expression of filamin A in invasive breast carcinoma and its significance. Tumor. 2009;29:659–62. Wu YP, Li JB, Zhao RJ, Zhao RJ, Wang XL, Shan BE, et al. Expression of filamin A in invasive breast carcinoma and its significance. Tumor. 2009;29:659–62.
16.
go back to reference Watanabe H. Extracellular matrix-regulation of cancer invasion and metastasis. Gan ToKagaku Ryoho. 2010;37:2058–61. Watanabe H. Extracellular matrix-regulation of cancer invasion and metastasis. Gan ToKagaku Ryoho. 2010;37:2058–61.
17.
go back to reference Yu HB, Zhang HF, Li DY, Zhang X, Xue HZ, Zhao SH. Matrine inhibits matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells. J Asian Nat Prod Res. 2011;13:242–50.PubMedCrossRef Yu HB, Zhang HF, Li DY, Zhang X, Xue HZ, Zhao SH. Matrine inhibits matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells. J Asian Nat Prod Res. 2011;13:242–50.PubMedCrossRef
18.
go back to reference Zhang M, Zhu GY, Gao HY, Zhao SP, Xue Y. Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in nasopharyngeal adenocarcinoma. J Surg Oncol. 2011;103:243–7.PubMedCrossRef Zhang M, Zhu GY, Gao HY, Zhao SP, Xue Y. Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in nasopharyngeal adenocarcinoma. J Surg Oncol. 2011;103:243–7.PubMedCrossRef
19.
go back to reference Yang S, Du J, Wang Z, Yuan W, Qiao Y, Zhang M, et al. BMP-6 promotes E-cadherin expression through repressing delta EF1 in breast cancer cells. BMC Cancer. 2007;7:211.PubMedCentralPubMedCrossRef Yang S, Du J, Wang Z, Yuan W, Qiao Y, Zhang M, et al. BMP-6 promotes E-cadherin expression through repressing delta EF1 in breast cancer cells. BMC Cancer. 2007;7:211.PubMedCentralPubMedCrossRef
20.
go back to reference Onoprishvili I, Ali S, Andria ML, Shpigel A, Simon EJ. Filamin A mutant lacking actin-binding domain restores mu opioid receptor regulation in melanoma cells. Neurochem Res. 2008;33:2054–61.PubMedCrossRef Onoprishvili I, Ali S, Andria ML, Shpigel A, Simon EJ. Filamin A mutant lacking actin-binding domain restores mu opioid receptor regulation in melanoma cells. Neurochem Res. 2008;33:2054–61.PubMedCrossRef
21.
go back to reference Zhu TN, He HJ, Kole S, D'Souza T, Agarwal R, Morin PJ, et al. Filamin A-mediated down-regulation of the exchange factor Ras-GRF1 correlates with decreased matrix metalloproteinase-9 expression in human melanoma cells. J Biol Chem. 2007;282:14816–26.PubMedCrossRef Zhu TN, He HJ, Kole S, D'Souza T, Agarwal R, Morin PJ, et al. Filamin A-mediated down-regulation of the exchange factor Ras-GRF1 correlates with decreased matrix metalloproteinase-9 expression in human melanoma cells. J Biol Chem. 2007;282:14816–26.PubMedCrossRef
22.
go back to reference He HJ, Kole S, Kwon YK, Crow MT, Bernier M. Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway. J Biol Chem. 2003;278:27096–104.PubMedCrossRef He HJ, Kole S, Kwon YK, Crow MT, Bernier M. Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway. J Biol Chem. 2003;278:27096–104.PubMedCrossRef
Metadata
Title
Filamin A regulates MMP-9 expression and suppresses prostate cancer cell migration and invasion
Authors
G. G. Sun
Y. F. Lu
J. Zhang
W. N. Hu
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1504-6

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