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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

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

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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