Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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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)
  • Published : 2014.02.01
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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.

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References

  1. Amin N, Vincan E (2012). The Wnt signaling pathways and cell adhesion. Front Biosci, 17, 784-804. https://doi.org/10.2741/3957
  2. 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.
  3. 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. https://doi.org/10.1371/journal.pone.0057393
  4. Bitler BG, Nicodemus JP, Li H, et al (2011). Wnt5a suppresses epithelial ovarian cancer by promoting cellular senescence. Cancer Res, 71, 6184-94. https://doi.org/10.1158/0008-5472.CAN-11-1341
  5. 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. https://doi.org/10.1038/sj.cr.7310078
  6. 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. https://doi.org/10.1242/dev.029025
  7. 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. https://doi.org/10.1016/j.cub.2009.07.062
  8. 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. https://doi.org/10.1158/0008-5472.CAN-10-0226
  9. Eisenberg CA, Eisenberg LM (1999). WNT11 promotes cardiac tissue formation of early mesoderm. Dev Dyn, 216, 45-58. https://doi.org/10.1002/(SICI)1097-0177(199909)216:1<45::AID-DVDY7>3.0.CO;2-L
  10. 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. https://doi.org/10.1161/CIRCULATIONAHA.107.741066
  11. 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.
  12. Kirikoshi H, Sekihara H, Katoh M (2001). Molecular cloning and characterization of human WNT11. Int J Mol Med, 8, 651-6.
  13. 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. https://doi.org/10.1074/jbc.M109.009654
  14. 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. https://doi.org/10.1242/dev.00520
  15. Matei D, Graeber TG, Baldwin RL, et al (2002). Gene expression in epithelial ovarian carcinoma. Oncogene, 21, 6289-98. https://doi.org/10.1038/sj.onc.1205785
  16. 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 https://doi.org/10.1074/jbc.M311724200
  17. McDonald SL, Silver A (2009). The opposing roles of Wnt-5a in cancer. Br J Cancer, 101, 209-14. https://doi.org/10.1038/sj.bjc.6605174
  18. 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. https://doi.org/10.1074/jbc.M804923200
  19. Mikels AJ, Nusse R (2006). Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol, 4, 115. https://doi.org/10.1371/journal.pbio.0040115
  20. 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. https://doi.org/10.1093/cvr/cvp254
  21. 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. https://doi.org/10.1074/jbc.M402877200
  22. 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. https://doi.org/10.1097/IGC.0b013e31820aaadb
  23. 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. https://doi.org/10.1006/dbio.1997.8745
  24. Pukrop T, Binder C (2008). The complex pathways of Wnt5a in cancer progression. J Mol Med, 86, 259-66. https://doi.org/10.1007/s00109-007-0266-2
  25. 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. https://doi.org/10.1016/j.yexcr.2008.04.010
  26. 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. https://doi.org/10.1210/endo.143.7.8908
  27. Tada M, Concha ML, Heisenberg CP (2002). Non-canonical Wnt signalling and regulation of gastrulation movements. Semin Cell Dev Biol, 13, 251-60. https://doi.org/10.1016/S1084-9521(02)00052-6
  28. 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. https://doi.org/10.1158/1541-7786.MCR-09-0238
  29. 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. https://doi.org/10.1038/sj.bjc.6605307
  30. 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. https://doi.org/10.1002/dvdy.23919
  31. 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.
  32. Uysal-Onganer P, Kypta RM (2011). Wnt11 in 2011 - the regulation and function of a non-canonical Wnt. Acta Physiologica, 204, 52-64.
  33. 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.
  34. 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. https://doi.org/10.1038/ng2112
  35. 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. https://doi.org/10.1158/0008-5472.CAN-04-2704

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