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Tumor Biology
Published in: Tumor Biology 12/2015

01-12-2015 | Research Article

Plakophilin 1-deficient cells upregulate SPOCK1: implications for prostate cancer progression

Authors: Cheng Yang, Regina Fischer-Kešo, Tanja Schlechter, Philipp Ströbel, Alexander Marx, Ilse Hofmann

Published in: Tumor Biology | Issue 12/2015

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Abstract

Plakophilin (PKP) 1 is frequently downregulated in prostate cancer and therefore may play a tumor-suppressive role. In the present study, we stably knocked down PKP1 in the non-neoplastic, prostatic BPH-1 cell line. In the PKP1-deficient cells, the expression of keratin 14 was lost, and the apoptosis rate was significantly reduced indicating that the cells acquired new biological capabilities. Moreover, we analyzed the gene expression profile of the PKP1-deficient BPH-1 cells. Among the genes that were significantly altered upon PKP1 knockdown, we noticed several extracellular matrix (ECM)-related genes and identified sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1/testican-1) as a gene of interest. SPOCK1 is a component of the ECM and belongs to a matricellular protein family named secreted protein, acidic, cysteine-rich (SPARC). The role of SPOCK1 in prostate cancer has not been clearly elucidated. We analyzed SPOCK1 mRNA expression levels in different cancer databases and characterized its expression in 136 prostatic adenocarcinomas by immunohistochemistry and western blot. SPOCK1 revealed a cytoplasmic localization in the glandular epithelium of the prostate and showed a significant upregulation of mRNA and protein in prostate tumor samples. Our findings support the hypothesis that PKP1 may have a tumor-suppressive function and suggest an important role of SPOCK1 in prostate tumor progression. Collectively, altered expression of PKP1 and SPOCK1 appears to be a frequent and critical event in prostate cancer.
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Literature
1.
Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61(6):1079–92.CrossRefPubMed
2.
Peifer M, Berg S, Reynolds AB. A repeating amino acid motif shared by proteins with diverse cellular roles. Cell. 1994;76(5):789–91.CrossRefPubMed
3.
Neuber S, Muhmer M, Wratten D, Koch PJ, Moll R, Schmidt A. The desmosomal plaque proteins of the plakophilin family. Dermatol Res Pract. 2010;2010:101452.PubMedPubMedCentral
4.
Garrod D, Chidgey M. Desmosome structure, composition and function. Biochim Biophys Acta. 2008;1778(3):572–87.CrossRefPubMed
5.
Bass-Zubek AE, Godsel LM, Delmar M, Green KJ. Plakophilins: multifunctional scaffolds for adhesion and signaling. Curr Opin Cell Biol. 2009;21(5):708–16.CrossRefPubMedPubMedCentral
6.
Wolf A, Krause-Gruszczynska M, Birkenmeier O, Ostareck-Lederer A, Huttelmaier S, Hatzfeld M. Plakophilin 1 stimulates translation by promoting eIF4A1 activity. J Cell Biol. 2010;188(4):463–71.CrossRefPubMedPubMedCentral
7.
Fischer-Keso R, Breuninger S, Hofmann S, Henn M, Rohrig T, Strobel P, et al. Plakophilins 1 and 3 bind to FXR1 and thereby influence the mRNA stability of desmosomal proteins. Mol Cell Biol. 2014;34(23):4244–56.CrossRefPubMedPubMedCentral
8.
Sobolik-Delmaire T, Katafiasz D, Keim SA, Mahoney MG, Wahl 3rd JK. Decreased plakophilin-1 expression promotes increased motility in head and neck squamous cell carcinoma cells. Cell Commun Adhes. 2007;14(2–3):99–109.CrossRefPubMed
9.
Papagerakis S, Shabana AH, Depondt J, Gehanno P, Forest N. Immunohistochemical localization of plakophilins (PKP1, PKP2, PKP3, and p0071) in primary oropharyngeal tumors: correlation with clinical parameters. Hum Pathol. 2003;34(6):565–72.CrossRefPubMed
10.
Kaz AM, Luo Y, Dzieciatkowski S, Chak A, Willis JE, Upton MP, et al. Aberrantly methylated PKP1 in the progression of Barrett’s esophagus to esophageal adenocarcinoma. Gene Chrom Cancer. 2012;51(4):384–93.CrossRef
11.
Schwarz J, Ayim A, Schmidt A, Jager S, Koch S, Baumann R, et al. Differential expression of desmosomal plakophilins in various types of carcinomas: correlation with cell type and differentiation. Hum Pathol. 2006;37(5):613–22.CrossRefPubMed
12.
Moll I, Kurzen H, Langbein L, Franke WW. The distribution of the desmosomal protein, plakophilin 1, in human skin and skin tumors. J Invest Dermatol. 1997;108(2):139–46.CrossRefPubMed
13.
Furukawa C, Daigo Y, Ishikawa N, Kato T, Ito T, Tsuchiya E, et al. Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer. Cancer Res. 2005;65(16):7102–10.CrossRefPubMed
14.
Aigner K, Descovich L, Mikula M, Sultan A, Dampier B, Bonne S, et al. The transcription factor ZEB1 (deltaEF1) represses plakophilin 3 during human cancer progression. FEBS Lett. 2007;581(8):1617–24.CrossRefPubMedPubMedCentral
15.
Valladares-Ayerbes M, Diaz-Prado S, Reboredo M, Medina V, Lorenzo-Patino MJ, Iglesias-Diaz P, et al. Evaluation of plakophilin-3 mRNA as a biomarker for detection of circulating tumor cells in gastrointestinal cancer patients. Cancer Epidemiol Biomarkers Prev. 2010;19(6):1432–40.CrossRefPubMed
16.
17.
Demirag GG, Sullu Y, Yucel I. Expression of plakophilins (PKP1, PKP2, and PKP3) in breast cancers. Med Oncol. 2012;29(3):1518–22.CrossRefPubMed
18.
Takahashi H, Nakatsuji H, Takahashi M, Avirmed S, Fukawa T, Takemura M, et al. Up-regulation of plakophilin-2 and down-regulation of plakophilin-3 are correlated with invasiveness in bladder cancer. Urology. 2012;79(1):240. e1–8.CrossRefPubMed
19.
Yang C, Strobel P, Marx A, Hofmann I. Plakophilin-associated RNA-binding proteins in prostate cancer and their implications in tumor progression and metastasis. Virchows Arch. 2013;463(3):379–90.CrossRefPubMed
20.
Breuninger S, Reidenbach S, Sauer CG, Strobel P, Pfitzenmaier J, Trojan L, et al. Desmosomal plakophilins in the prostate and prostatic adenocarcinomas: implications for diagnosis and tumor progression. Am J Pathol. 2010;176(5):2509–19.CrossRefPubMedPubMedCentral
21.
Schaefer L, Schaefer RM. Proteoglycans: from structural compounds to signaling molecules. Cell Tissue Res. 2010;339(1):237–46.CrossRefPubMed
22.
Jarvelainen H, Sainio A, Koulu M, Wight TN, Penttinen R. Extracellular matrix molecules: potential targets in pharmacotherapy. Pharmacol Rev. 2009;61(2):198–223.CrossRefPubMedPubMedCentral
23.
24.
25.
Bode W, Huber R. Proteinase-protein inhibitor interaction. In: Sies H, Flohé L, Zimmer G, editors. Molecular aspects of inflammation. Colloquium der gesellschaft für biologische chemie 11–13 April 1991 in Mosbach/Baden. Heidelberg: Springer Berlin; 1991. p. 103–15.
26.
27.
28.
Tai IT, Tang MJ. SPARC in cancer biology: its role in cancer progression and potential for therapy. Drug Resist Updat. 2008;11(6):231–46.CrossRefPubMed
29.
Li Y, Chen L, Chan TH, Liu M, Kong KL, Qiu JL, et al. SPOCK1 is regulated by CHD1L and blocks apoptosis and promotes HCC cell invasiveness and metastasis in mice. Gastroenterology. 2013;144(1):179–91. e4.CrossRefPubMed
30.
Leja J, Essaghir A, Essand M, Wester K, Oberg K, Totterman TH, et al. Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Mod Pathol. 2009;22(2):261–72.CrossRefPubMed
31.
Kim HP, Han SW, Song SH, Jeong EG, Lee MY, Hwang D, et al. Testican-1-mediated epithelial-mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer. Oncogene. 2014;33(25):3334–41.CrossRefPubMed
32.
Wlazlinski A, Engers R, Hoffmann MJ, Hader C, Jung V, Muller M, et al. Downregulation of several fibulin genes in prostate cancer. Prostate. 2007;67(16):1770–80.CrossRefPubMed
33.
Epstein JI, Allsbrook Jr WC, Amin MB, Egevad LL. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol. 2005;29(9):1228–42.CrossRefPubMed
34.
Hayward SW, Dahiya R, Cunha GR, Bartek J, Deshpande N, Narayan P. Establishment and characterization of an immortalized but non-transformed human prostate epithelial cell line: BPH-1. In Vitro Cell Dev Biol Anim. 1995;31(1):14–24.CrossRefPubMed
35.
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):l1.CrossRef
36.
Stamenkovic I. Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol. 2003;200(4):448–64.CrossRefPubMed
37.
Krojer T, Garrido-Franco M, Huber R, Ehrmann M, Clausen T. Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine. Nature. 2002;416(6879):455–9.CrossRefPubMed
38.
Clements J, Hooper J, Dong Y, Harvey T. The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions. Biol Chem. 2001;382(1):5–14.CrossRefPubMed
39.
40.
Bobek LA, Levine MJ. Cystatins—inhibitors of cysteine proteinases. Crit Rev Oral Biol Med. 1992;3(4):307–32.CrossRefPubMed
41.
42.
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401–4.CrossRefPubMed
43.
Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010;18(1):11–22.CrossRefPubMedPubMedCentral
44.
Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, et al. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 2007;9(2):166–80.CrossRefPubMedPubMedCentral
45.
Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, et al. Oncomine: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004;6(1):1–6.CrossRefPubMedPubMedCentral
46.
Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, et al. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci U S A. 2004;101(3):811–6.CrossRefPubMedPubMedCentral
47.
48.
Green KJ, Simpson CL. Desmosomes: new perspectives on a classic. J Invest Dermatol. 2007;127(11):2499–515.CrossRefPubMed
49.
50.
51.
van Leenders GJ, Aalders TW, de Kaa CA H-v, Ruiter DJ, Schalken JA. Expression of basal cell keratins in human prostate cancer metastases and cell lines. J Pathol. 2001;195(5):563–70.CrossRefPubMed
52.
Okada H, Tsubura A, Okamura A, Senzaki H, Naka Y, Komatz Y, et al. Keratin profiles in normal/hyperplastic prostates and prostate carcinoma. Virchows Arch A Pathol Anat Histopathol. 1992;421(2):157–61.CrossRefPubMed
53.
Ke XS, Li WC, Hovland R, Qu Y, Liu RH, McCormack E, et al. Reprogramming of cell junction modules during stepwise epithelial to mesenchymal transition and accumulation of malignant features in vitro in a prostate cell model. Exp Cell Res. 2011;317(2):234–47.CrossRefPubMed
54.
55.
Alliel PM, Perin JP, Jolles P, Bonnet FJ. Testican, a multidomain testicular proteoglycan resembling modulators of cell social behaviour. Eur J Biochem. 1993;214(1):347–50.CrossRefPubMed
56.
Wight TN, Kinsella MG, Qwarnstrom EE. The role of proteoglycans in cell adhesion, migration and proliferation. Curr Opin Cell Biol. 1992;4(5):793–801.CrossRefPubMed
57.
Manon-Jensen T, Itoh Y, Couchman JR. Proteoglycans in health and disease: the multiple roles of syndecan shedding. FEBS J. 2010;277(19):3876–89.CrossRefPubMed
58.
Edgell CJ, BaSalamah MA, Marr HS. Testican-1: a differentially expressed proteoglycan with protease inhibiting activities. Int Rev Cytol. 2004;236:101–22.CrossRefPubMed
59.
Bocock JP, Edgell CJ, Marr HS, Erickson AH. Human proteoglycan testican-1 inhibits the lysosomal cysteine protease cathepsin L. Eur J Biochem. 2003;270(19):4008–15.CrossRefPubMed
60.
Marr HS, Edgell CJ. Testican-1 inhibits attachment of Neuro-2a cells. Matrix Biol. 2003;22(3):259–66.CrossRefPubMed
61.
Miao L, Wang Y, Xia H, Yao C, Cai H, Song Y. SPOCK1 is a novel transforming growth factor-β target gene that regulates lung cancer cell epithelial-mesenchymal transition. Biochem Biophys Res Commun. 2013;440(4):792–7.CrossRefPubMed
62.
Pieters T, van Roy F, van Hengel J. Functions of p120ctn isoforms in cell-cell adhesion and intracellular signaling. Front Biosci. 2012;17:1669–94.CrossRef
63.
64.
De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013;13(2):97–110.CrossRefPubMed
65.
Aparicio LA, Abella V, Valladares M, Figueroa A. Posttranscriptional regulation by RNA-binding proteins during epithelial-to-mesenchymal transition. Cell Mol Life Sci. 2013;70(23):4463–77.CrossRefPubMedPubMedCentral
Metadata
Title
Plakophilin 1-deficient cells upregulate SPOCK1: implications for prostate cancer progression
Authors
Cheng Yang
Regina Fischer-Kešo
Tanja Schlechter
Philipp Ströbel
Alexander Marx
Ilse Hofmann
Publication date
01-12-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3628-3

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