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http://dx.doi.org/10.7314/APJCP.2014.15.3.1489

Differential Wnt11 Expression Related to Wnt5a in High- and Low-grade Serous Ovarian Cancer: Implications for Migration, Adhesion and Survival  

Jannesari-Ladani, Farnaz (Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, University College of Science, University of Tehran)
Hossein, Ghamartaj (Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, University College of Science, University of Tehran)
Izadi-Mood, Narges (Department of Pathology, Mirza Koochak Khan Hospital, Tehran University of Medical Sciences)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.3, 2014 , pp. 1489-1495 More about this Journal
Abstract
Wnt is a powerful signaling pathway that plays a crucial role in cell fate determination, survival, proliferation and motility during development, in adult tissues and cancer. The aims of the present study were three fold: i) to assess Wnt11 immunoexpression and its possible relationship with Wnt5a in high- and low-grade human serous ovarian cancer (HGSC and LGSC) specimens; ii) to assess Wnt11 expression levels in Wnt5a overexpressing SKOV-3 cells; iii) to reveal the role of Wnt11 in viability, adhesion, migration and invasion of SKOV-3 cells using recombinant human Wnt11 (rhWnt11). Immunohistochemistry revealed a significant difference in Wnt11 expression between HGSC and LGSC groups (p=0.001). Moreover, a positive correlation was observed between Wnt5a and Wnt11 expression in the HGSC (r=0.713, p=0.001), but not the LGSC group. The expression of Wnt11 was decreased by 35% in Wnt5a overexpressing cells (SKOV-3/Wnt5a) compared to mock controls. Similarly Wnt11 expression levels were decreased by 47% in the presence of exogenous Wnt5a compared to untreated cells. In the presence of rhWnt11, 31% increased cell viability (p<0.001) and 21% increased cell adhesion to matrigel (p<0.01) were observed compared to control. Cell migration was increased by 1.6-fold with rhWnt11 as revealed by transwell migration assay (p<0.001). However, 45% decreased cell invasion was observed in the presence of rhWnt11 compared to control (p<0.01). Our results may suggest that differential Wnt11 immunoexpression in HGSC compared to LGSC could play important roles in serous ovarian cancer progression and may be modulated by Wnt5a expression levels.
Keywords
Epithelial ovarian cancer; Wnt11; Wnt5a; adhesion; migration; viability;
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1 Usongo M, Li X, Farookhi R (2013). Activation of the canonical WNT signaling pathway promotes ovarian surface epithelial proliferation without inducing ${\beta}$-catenin/Tcf-mediated reporter expression. Dev Dyn, 242, 291-300.   DOI   ScienceOn
2 Tada M, Concha ML, Heisenberg CP (2002). Non-canonical Wnt signalling and regulation of gastrulation movements. Semin Cell Dev Biol, 13, 251-60.   DOI   ScienceOn
3 Toyama T, Lee HC, Koga H, Wands JR, Kim M (2010). Non-canonical Wnt11 inhibits hepatocellular carcinoma cell proliferation and migration. Mol Cancer Res, 8, 254-65.   DOI
4 Ueno K, Hazama S, Mitomori S, et al (2009). Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells. Br J Cancer, 101, 1374-81.   DOI   ScienceOn
5 Uysal-Onganer P, Kawano Y, Caro M, et al (2010). Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells. Mol Cancer, 10, 9-55.
6 Uysal-Onganer P, Kypta RM (2011). Wnt11 in 2011 - the regulation and function of a non-canonical Wnt. Acta Physiologica, 204, 52-64.
7 Yuzugullu H, Benhaj K, Ozturk N, et al (2009). Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells. Mol Cancer, 22, 8-90.
8 Zhou W, Lin L, Majumdar A, et al (2007). Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2. Nat Genet, 39, 1225-34.   DOI   ScienceOn
9 Zhu H, Mazor M, Kawano Y, et al (2004). Analysis of Wnt gene expression in prostate cancer: mutual inhibition by WNT11 and the androgen receptor. Cancer Res, 64, 7918-26.   DOI   ScienceOn
10 Nagy II, Railo A, Rapila R, et al (2010). Wnt-11 signalling controls ventricular myocardium development by patterning N-cadherin and beta-catenin expression. Cardiovasc Res, 85, 100-9.   DOI
11 McDonald SL, Silver A (2009). The opposing roles of Wnt-5a in cancer. Br J Cancer, 101, 209-14.   DOI
12 Peng C, Zhang X, Yu H, Wu D, Zheng J (2011). Wnt5a as a predictor in poor clinical outcome of patients and a mediator in chemoresistance of ovarian cancer. Int Gynecol Cancer, 21, 280-8.   DOI
13 Medrek C, Landberg G, Andersson T, Leandersson K (2009). Wnt-5a-CKI{alpha} signaling promotes {beta}-catenin/E-cadherin complex formation and intercellular adhesion in human breast epithelial cells. J Biol Chem, 284, 10968-79.   DOI
14 Mikels AJ, Nusse R (2006). Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol, 4, 115.   DOI
15 Ouko L, Ziegler TR, Gu LH, Eisenberg LM, Yang VW (2004). Wnt11 signaling promotes proliferation, transformation, and migration of IEC6 intestinal epithelial cells. J Biol Chem, 279, 26707-15.   DOI
16 Pepicelli CV, Kispert A, Rowitch DH, Mcmahon AP (1997). GDNF induces branching and increased cell proliferation in the ureter of the mouse. Dev Biol, 192, 193-8.   DOI
17 Pukrop T, Binder C (2008). The complex pathways of Wnt5a in cancer progression. J Mol Med, 86, 259-66.   DOI
18 Railo A, Nagy II, Kilpelainen P, Vainio S (2008). Wnt-11 signaling leads to downregulation of the Wnt/beta-catenin, JNK/AP-1 and NF-kappaB pathways and promotes viability in the CHO-K1 cells. Exp Cell Res, 314, 2389-99.   DOI
19 Ricken A, Lochhead P, Kontogiannea M, Farookhi R (2002). Wnt signaling in the ovary: Identification and compartmentalized expression of -Wnt-2, Wnt-2b and frizzled-4 mRNAs. Endocrinology, 143, 2741-9.   DOI
20 Flaherty MP, Abdel-Latif A, Li Q, et al (2008). Noncanonical Wnt11 signaling is sufficient to induce cardiomyogenic differentiation in unfractionated bone marrow mononuclear cells. Circulation, 117, 2241-52.   DOI
21 Katoh M (2009). Integrative genomic analyses of WNT11: transcriptional mechanisms based on canonical WNT signals and GATA transcription factors signaling. Int J Mol Med, 24, 247-51.
22 Cha SW, Tadjuidje E, White J, et al (2009). Wnt11/5a complex formation caused by tyrosine sulfation increases canonical signaling activity. Curr Biol, 19, 1573-80.   DOI
23 Dwyer MA, Joseph JD, Wade HE, et al (2010). WNT11 expression is induced by estrogen-related receptor ${\alpha}$ and ${\beta}$-catenin and acts in an autocrine manner to increase cancer cell migration. Cancer Res, 70, 9298-308.   DOI
24 Eisenberg CA, Eisenberg LM (1999). WNT11 promotes cardiac tissue formation of early mesoderm. Dev Dyn, 216, 45-58.   DOI
25 Kirikoshi H, Sekihara H, Katoh M (2001). Molecular cloning and characterization of human WNT11. Int J Mol Med, 8, 651-6.
26 Liu JX, Hu B, Wang Y, Gui JF, Xiao W (2009). Zebrafish eaf1 and eaf2/u19 mediate effective convergence and extension movements through the maintenance of wnt11 and wnt5 expression. J Biol Chem, 284, 16679-92.   DOI
27 Majumdar A, Vainio S, Kispert A, McMahon J, McMahon AP (2003). Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development, 130, 3175-85.   DOI   ScienceOn
28 Matei D, Graeber TG, Baldwin RL, et al (2002). Gene expression in epithelial ovarian carcinoma. Oncogene, 21, 6289-98.   DOI
29 Amin N, Vincan E (2012). The Wnt signaling pathways and cell adhesion. Front Biosci, 17, 784-804.   DOI
30 Badiglian Filho L, Oshima CT, De Oliveira Lima F, et al (2009). Canonical and noncanonical Wnt pathway: a comparison among normal ovary, benign ovarian tumor and ovarian cancer. Oncol Rep, 21, 313-20.
31 Bartis D, Csongei V, Weich A, et al (2013). Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma. PLoS One, 8, 57393.   DOI
32 Bitler BG, Nicodemus JP, Li H, et al (2011). Wnt5a suppresses epithelial ovarian cancer by promoting cellular senescence. Cancer Res, 71, 6184-94.   DOI
33 Cao Q, Lu X, Feng YJ (2006). Glycogen synthase kinase-3beta positively regulates the proliferation of human ovarian cancer cells. Cell Res, 16, 671-7.   DOI
34 Cha SW, Tadjuidje E, Tao Q, Wylie C, Heasman J (2008). Wnt5a and Wnt11 interact in a maternal Dkk1-regulated fashion to activate both canonical and non-canonical signaling in Xenopus axis formation. Development, 135, 3719-29.   DOI
35 Maye P, Zheng J, Li L, Wu D (2004). Multiple mechanisms for Wnt11-mediated repression of the canonical Wnt signaling pathway. J Biol Chem, 279, 24659-65   DOI