Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Pathology & Oncology Research
Published in: Pathology & Oncology Research 2/2015

01-04-2015 | Research

The Evaluation of WBP2NL-Related Genes Expression in Breast Cancer

Authors: Seyedmehdi Nourashrafeddin, Mahmoud Aarabi, Mohammad Hosein Modarressi, Marveh Rahmati, Mohammad Nouri

Published in: Pathology & Oncology Research | Issue 2/2015

Login to get access

Abstract

Breast cancer is the most frequent cause of mortality in women all around the world; therefore, study on molecular aspects of breast cancer is necessary for finding new biomarkers. Recent studies have shown that WW Binding Protein 2 (WBP2) is an important protein for the oncogenic property of cancer. We have previously evaluated the WW Binding Protein 2 N-Terminal Like (WBP2NL) gene expression in cancerous cell line and breast tumor tissues, and reported changes in expression, which could increase tumorigenic cell growth. However, the molecular mechanisms of WBP2NL and its clinical relevance have not been investigated. In this study, the expression of WBP2NL-related genes in the invasive breast carcinoma and normal breast tissues was evaluated for the first time. Analysis of WBP2NL-related genes expression was performed with reverse transcription-PCR and real time-PCR detection method. The target genes studied were as follow: WW domain containing E3 ubiquitin protein ligase 1(WWP1), membrane associated guanylatekinase containing WW and PDZ domain-1 (MAGI1), neural precursor cell expressed developmentally down-regulated 4 (NEDD4), formin binding protein-4 (FNBP4), BCL2-associated athanogene-3 (BAG3), WW domain-containing oxidoreductase (WWOX), yes-associated protein-1 (YAP1), WW domain containing transcription regulator (WWTR1), member RAS oncogene family (RAB2A), and small G protein signaling modulator 3 (SGSM3). The expression of WWP1, BAG3, and WWTR1 was significantly increased in breast cancer. In contrast, the expression of WWOX, YAP1, RAB2A, and SGSM3 was significantly decreased. The MAGI1 and NEDD4 expression was increased, while the expression of FNBP4 was unchanged. These findings lead us to suggest that WBP2NL might play roles as an anti-apoptotic factor or co-activator to promote breast cancer cell survival and proliferation.
Literature
1.
Patsialou A, Wang Y, Lin J, Whitney K, Goswami S, Kenny PA, Condeelis JS (2012) Selective gene-expression profiling of migratory tumor cells in vivo predictsclinical outcome in breast cancer patients. Breast Cancer Res 14(5):R139CrossRefPubMedCentralPubMed
2.
Key TJ, Verkasalo PK, Banks E (2001) Epidemiology of breast cancer. The Lancet Oncology 2(3):133–140CrossRefPubMed
3.
Nishidate T, Katagiri T, Lin ML, Mano Y, Miki Y, Kasumi F, Yoshimoto M, Tsunoda T, Hirata K, Nakamura Y (2004) Genome-wide gene-expression profiles of breast-cancer cells purified with laser microbeam microdissection: identification of genes associated with progression and metastasis. Int J Oncol 25(4):797–819PubMed
4.
Chen HI, Sudol M (1995) The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Proc Natl Acad Sci U S A 92(17):7819–23CrossRefPubMedCentralPubMed
5.
Sudol M, Chen HI, Bougeret C, Einbond A, Bork P (1995) Characterization of a novel protein-binding module—the WW domain. FEBS Lett 369:67–71CrossRefPubMed
6.
Komuro A, Nagai M, Navin NE, Sudol M (2003) WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem 278:33334–33341CrossRefPubMed
7.
Overholtzer M, Zhang J, Smolen GA, Muir B, Li W, Sgroi DC, Deng CX, Brugge JS, Haber DA (2006) Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci USA 103:12405–12410CrossRefPubMedCentralPubMed
8.
9.
10.
Macias MJ, Wiesner S, Sudol M (2002) WW and SH3 domains, two different scaffolds to recognize proline-rich ligands. FEBS Lett 513(1):30–7CrossRefPubMed
11.
McDonald CB, McIntosh SK, Mikles DC, Bhat V, Deegan BJ, Seldeen KL, Saeed AM, Buffa L, Sudol M, Nawaz Z, Farooq A (2011) Biophysical analysis of binding of WW domains of the YAP2 transcriptional regulator to PPXY motifs within WBP1 and WBP2 adaptors. Biochemistry 50:9616–9627CrossRefPubMedCentralPubMed
12.
Wang K, Degerny C, Xu M, Yang XJ (2009) YAP, TAZ, and Yorkie: a conserved family of signal-responsive transcriptional coregulators in animal development and human disease. Biochem Cell Biol 87(1):77–91CrossRefPubMed
13.
Chan SW, Lim C, Huang C, Chong YF, Gunaratne HJ, Hogue KA, Blackstock WP, Harvey KF, Hong W (2011) WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ. Oncogene 30:600–610CrossRefPubMedCentralPubMed
14.
de Cristofaro T, Di Palma T, Ferraro A, Corrado A, Lucci V, Franco R, Fusco A, Zannini M (2011) TAZ/ WWTR1 is overexpressed in papillary thyroid carcinoma. Eur J Cancer 47:926–33CrossRefPubMed
15.
15- Wang L, Chen Z, Wang Y, Chang D, Su L, Guo Y, Liu C (2013) WWTR1 promotes cell proliferation and inhibits apoptosis through cyclin A and CTGF regulation in non-small cell lung cancer. Tumour Biol. [Epub ahead of print]
16.
17.
Zhang X, Milton CC, Poon CL, Hong W, Harvey KF (2011) Wbp2 cooperates with yorkie to drive tissue growth downstream of the Salvador-warts-hippo pathway. Cell Death Differ 18(8):1346–55CrossRefPubMedCentralPubMed
18.
Wu AT, Sutovsky P, Xu W, Vander Spoel AC, Platt FM, Oko R (2007) The postacrosomal assembly of sperm head protein, PAWP, is independent of acrosome formation and dependent on microtubular manchette transport. Dev Biol 312(2):471–83CrossRefPubMed
19.
Sutovsky P, Manandhar G, Wu A, Oko R (2003) Interactions of sperm perinuclear theca with the oocyte: implications for oocyte activation, anti-polyspermy defense, and assisted reproduction. Microsc Res Tech 61(4):362–78CrossRefPubMed
20.
Wu AT, Sutovsky P, Manandhar G, Xu W, Katayama M, Day BN, Park KW, Yi YJ, Xi YW, Prather RS, Oko R (2007) PAWP, A sperm specific ww-domain binding protein, promotes meiotic resumption and pronuclear development during fertilization. J Biol Chem 282(16):12164–75CrossRefPubMed
21.
Oko R, Sutovsky P (2009) Biogenesis of sperm perinuclear theca and its role in sperm functional competence and fertilization. J Reprod Immunol 83(1–2):2–7CrossRefPubMed
22.
Aarabi M, Qin Z, Xu W, Mewburn J, Oko R (2010) Sperm-borne protein, PAWP, initiates zygotic development in Xenopus laevis by eliciting intracellular calcium release. Mol Reprod Dev 77(3):249–56PubMed
23.
Nourashrafeddin S, Aarabi M, Miryounesi M, Ebrahimzadeh-Vesal R, Zarghami N, Modarressi MH, Nouri M (2014) Expression analysis of PAWP during mouse embryonic stem cell-based spermatogenesis in vitro. Vitro Cell Dev Biol Anim 50(5):475–81CrossRef
24.
Györffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, Szallasi Z (2010) An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat 123:725–731CrossRefPubMed
25.
von Mering C, Jensen LJ, Kuhn M, Chaffron S, Doerks T, Kruger B, Snel B, Bork P (2007) STRING 7 - recent developments in the integration and prediction of protein interactions. Nucleic Acids Res 35:D358–D362CrossRef
26.
Dhananjayan SC, Ramamoorthy S, Khan OY, Ismail A, Sun J, Slingerland J, O’Malley BW, Nawaz Z (2006) WW domain binding protein-2, an E6-assoiated protein interacting protein, acts as a coactivator of estrogen and progesterone recep- tors. Mol Endocrinol 20:2343–54CrossRefPubMed
27.
Lim SK, Orhant-Prioux M, Toy W, Tan KY, Lim YP (2011) Tyrosine phosphorylation of transcriptional coactivator WW-domain binding protein 2 regulates estrogen receptor α function in breast cancer via the Wnt pathway. FASEB J 25(9):3004–18CrossRefPubMed
28.
Buffa L, Saeed AM, Nawaz Z (2013) Molecular mechanism of WW-domain binding protein-2 coactivation function in estrogen receptor signaling. IUBMB Life 65(1):76–84CrossRefPubMed
29.
Xie M, Zhang L, He CS, Hou JH, Lin SX, Hu ZH, Xu F, Zhao HY (2012) Prognostic significance of TAZ expression in resected non-small cell lung cancer. J Thorac Oncol 7(5):799–807CrossRefPubMed
30.
Zhou Z, Hao Y, Liu N, Raptis L, Tsao MS, Yang X (2011) TAZ is a novel oncogene in non-small cell lung cancer. Oncogene 30(18):2181–6CrossRefPubMed
31.
Chan SW, Lim CJ, Guo K, Ng CP, Lee I, Hunziker W, Zeng Q, Hong W (2008) A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells. Cancer Res 68(8):2592–8CrossRefPubMed
32.
Chen C, Sun X, Guo P, Dong XY, Sethi P, Zhou W et al (2007) Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer. Oncogene 26:2386–2394CrossRefPubMed
33.
Li Y, Zhou Z, Alimandi M, Chen C (2009) WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer. Oncogene 28(33):2948–58CrossRefPubMed
34.
Zhao D, Zhi X, Zhou Z, Chen C (2012) TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis. Carcinogenesis 33(1):59–67CrossRefPubMed
35.
36.
Chen Y, Yang LN, Cheng L, Tu S, Guo SJ, Le HY, Xiong Q, Mo R, Li CY, Jeong JS, Jiang L, Blackshaw S, Bi LJ, Zhu H, Tao SC, Ge F (2013) BAG3 interactome analysis reveals a new role in modulating proteasome activity. Mol Cell Proteomics 12(10):2804–19CrossRefPubMedCentralPubMed
37.
Boiani M, Daniel C, Liu X, Hogarty MD, Marnett LJ (2013) The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. J Biol Chem 288(10):6980–90CrossRefPubMedCentralPubMed
38.
Qu J, Lu W, Li B, Lu C, Wan X (2013) WWOX induces apoptosis and inhibits proliferation in cervical cancer and cell lines. Int J Mol Med 31(5):1139–47PubMed
39.
Göthlin Eremo A, Wegman P, Stål O, Nordenskjöld B, Fornander T, Wingren S (2013) Wwox expression may predict benefit from adjuvant tamoxifen in randomized breast cancer patients. Oncol Rep 29(4):1467–74PubMed
40.
Yang H, Sasaki T, Minoshima S, Shimizu N (2007) Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway. Genomics 90(2):249–60CrossRefPubMed
41.
Chia WJ, Tang BL (2009) Emerging roles for Rab family GTPases in human cancer. Biochim Biophys Acta 1795:110–6PubMed
42.
Diep CH, Zucker KM, Hostetter G, Watanabe A, Hu C, Munoz RM, Von Hoff DD, Han H (2012) Down-regulation of yes associated protein 1 expression reduces cell proliferation and clonogenicity of pancreatic cancer cells. PLoS One 7(3):e32783CrossRefPubMedCentralPubMed
43.
Yuan M, Tomlinson V, Lara R, Holliday D, Chelala C, Harada T, Gangeswaran R, Manson-Bishop C, Smith P, Danovi SA, Pardo O, Crook T, Mein CA, Lemoine NR, Jones LJ, Basu S (2008) Yes-associated protein (YAP) functions as a tumor suppressor in breast. Cell Death Differ 15:1752–1759CrossRefPubMed
44.
45.
Stenmark H (2009) Rab GTPases as coordinators of vesicle traffic. Nature Rev Mol Cell Biol 10:513–525CrossRef
46.
Mosesson Y, Mills GB, Yarden Y (2008) Derailed endocytosis: an emerging feature of cancer. Nature Rev Cancer 8(11):835–850CrossRef
47.
Mountjoy JR, Xu W, McLeod D, Hyndman D, Oko R (2008) RAB2A: a major subacrosomal protein of bovine spermatozoa implicated in acrosomal biogenesis. Biol Reprod 79(2):223–32CrossRefPubMed
48.
Wang X, Trotman LC, TKoppie T, Alimonti A, Chen Z, Gao Z, Wang J, Erdjument-Bromage H, Tempst P, Cordon Cardo C, Pandolfi PP, Jiang X (2007) NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 128(1):129–39CrossRefPubMedCentralPubMed
49.
Amodio N, Scrima M, Palaia L, Salman AN, Quintiero A, Franco R, Botti G, Pirozzi P, Rocco G, De Rosa N, Viglietto G (2010) Oncogenic role of the E3 ubiquitin ligase NEDD4–1, a PTEN negative regulator, in non-small-cell lung carcinomas. Am J Pathol 177(5):2622–34CrossRefPubMedCentralPubMed
50.
Wong KA, Wilson J, Russo A, Wang L, Okur MN, Wang X, Martin NP, Scappini E, Carnegie GK, O’Bryan JP (2012) Intersectin (ITSN) family of scaffolds function as molecular hubs in protein interaction networks. PLoS One 7(4):e36023CrossRefPubMedCentralPubMed
51.
Kondo Y, Koshimizu E, Megarbane A, Hamanoue H, Okada I, Nishiyama K, Kodera H, Miyatake S, Tsurusaki Y, Nakashima M, Doi H, Miyake N, Saitsu H, Matsumoto N (2013) Whole-exome sequencing identified a homozygous FNBP4 mutation in a family with a condition similar to microphthalmia with limb anomalies. Am J Med Genet A 161A(7):1543–6CrossRefPubMed
52.
Zhang G, Wang Z (2011) MAGI1 inhibits cancer cell migration and invasion of hepatocellular carcinoma via regulating PTEN. Zhong Nan Da Xue Xue Bao Yi Xue Ban 36(5):381–5PubMed
Metadata
Title
The Evaluation of WBP2NL-Related Genes Expression in Breast Cancer
Authors
Seyedmehdi Nourashrafeddin
Mahmoud Aarabi
Mohammad Hosein Modarressi
Marveh Rahmati
Mohammad Nouri
Publication date
01-04-2015
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2015
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-014-9820-8

Other articles of this Issue 2/2015

Pathology & Oncology Research 2/2015 Go to the issue

Research

Mutations in G Protein Encoding Genes and Chromosomal Alterations in Primary Leptomeningeal Melanocytic Neoplasms

Research

Association of P53 (−16ins-Pro) Haplotype with the Decreased Risk of Differentiated Thyroid Carcinoma in Iranian-Azeri Patients

Research

Survivin mRNA Level in Blood Predict the Efficacy of Neoadjuvant Chemotherapy in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer

Research

CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation

Research

Immunohistochemical Study of Glypican-3 and HepPar-1 in Differentiating Hepatocellular Carcinoma from Metastatic Carcinomas in FNA of the Liver

Research

Identification of Differently Expressed Genes with Specific SNP Loci for Breast Cancer by the Integration of SNP and Gene Expression Profiling Analyses
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits