The Wnt5a/Ror2 noncanonical signaling pathway inhibits canonical Wnt signaling in K562 cells

  • Authors:
    • Yuan Yuan
    • Chang Chun Niu
    • Gang Deng
    • Zhao Quan Li
    • Jing Pan
    • Chen Zhao
    • Zong Lin Yang
    • Wei Ke Si
  • View Affiliations

  • Published online on: November 10, 2010     https://doi.org/10.3892/ijmm.2010.560
  • Pages: 63-69
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Abstract

Wnt5a has been shown to be involved in cancer progression in a variety of tumor types, and regulates multiple intracellular signaling cascades; it is a representative ligand that activates a noncanonical Wnt signaling pathway. The mechanism governing how Wnt5a determines the specificity of these pathways and the relationship with tumorigenesis is still unknown. In this study, we aimed to clarify the tumor suppressor role of Wnt5a in leukemogenesis. In particular, we focused on Ror2 functioning as a Wnt5a receptor to mediate noncanonical Wnt signaling, which inhibits canonical Wnt signaling in K562 cells. We found that up-regulation of Wnt5a expression increased Ror2 expression in K562 cells and Wnt5a and Ror2 were co-expressed in the cytoplasm. Also, Wnt5a induced the intrnalization of Ror2. Co-immunoprecipitation experiments were performed to determine whether Ror2 binds to Wnt5a, and inhibits Wnt5a binding with Frizzled4 and LRP5 in Wnt5a treated K562 cells. Wnt5a had no effect on total ß-catenin expression levels, but regulated tyrosine phosphorylation of ß-catenin and translocation of ß-catenin from the cytoplasm to the nucleus. Furthermore, expression of Wnt5a was associated with suppression of ß-catenin/TCF-dependent transcriptional activity and down-regulated the expression of cyclin D1, a downstream target gene of the canonical Wnt signaling pathway. We hypothesize that Wnt5a plays the role of a tumor suppressor in leukemogenesis through the Wnt5a/Ror2 noncanonical signaling pathway that inhibits Wnt canonical signaling.

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January 2011
Volume 27 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yuan Y, Niu CC, Deng G, Li ZQ, Pan J, Zhao C, Yang ZL and Si WK: The Wnt5a/Ror2 noncanonical signaling pathway inhibits canonical Wnt signaling in K562 cells. Int J Mol Med 27: 63-69, 2011
APA
Yuan, Y., Niu, C.C., Deng, G., Li, Z.Q., Pan, J., Zhao, C. ... Si, W.K. (2011). The Wnt5a/Ror2 noncanonical signaling pathway inhibits canonical Wnt signaling in K562 cells. International Journal of Molecular Medicine, 27, 63-69. https://doi.org/10.3892/ijmm.2010.560
MLA
Yuan, Y., Niu, C. C., Deng, G., Li, Z. Q., Pan, J., Zhao, C., Yang, Z. L., Si, W. K."The Wnt5a/Ror2 noncanonical signaling pathway inhibits canonical Wnt signaling in K562 cells". International Journal of Molecular Medicine 27.1 (2011): 63-69.
Chicago
Yuan, Y., Niu, C. C., Deng, G., Li, Z. Q., Pan, J., Zhao, C., Yang, Z. L., Si, W. K."The Wnt5a/Ror2 noncanonical signaling pathway inhibits canonical Wnt signaling in K562 cells". International Journal of Molecular Medicine 27, no. 1 (2011): 63-69. https://doi.org/10.3892/ijmm.2010.560