Phosphorylation of β-catenin results in lack of β-catenin signaling in melanoma

  • Authors:
    • Silke Kuphal
    • Anja Katrin Bosserhoff
  • View Affiliations

  • Published online on: May 3, 2011     https://doi.org/10.3892/ijo.2011.1028
  • Pages: 235-243
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Abstract

The Wnt/β-catenin pathway is involved in differentiation events during embryonic development and is further described as a pathway often participating in tumor formation when aberrantly activated. Molecular studies concentrating on colorectal cancer revealed mutations of apc, ctnnbi, btrc and tcf-4 genes which mimic Wnt stimulation. However, such mutations are rarely found during melanoma development. Therefore, we analyzed the β-catenin activity in this type of skin cancer. Interestingly, localization of β-catenin protein was basically cytoplasmic in melanomas in vivo, which was in clear contrast to findings in colon carcinoma. Congruently, the transcriptional activity of β-catenin regulating expression of β-catenin target genes was not observed in several melanoma cell lines. Further, neither LiCl nor Wnt agonist treatment led to significant activation of β-catenin signaling. This lack in functionality seems to depend on phosphorylation at threonine 41 and serine 45 of β-catenin observed in several melanoma cell lines. However, this specific endogenous phosphorylation pattern led to upregulation of other signaling pathways resulting e.g. in induction of N-cadherin expression. In summary, this study suggests a cell type-specific regulation of β-catenin function. This alternative β-catenin signaling pathway should be considered when thinking about targeting β-catenin in melanoma treatment.

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July 2011
Volume 39 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kuphal S and Kuphal S: Phosphorylation of β-catenin results in lack of β-catenin signaling in melanoma. Int J Oncol 39: 235-243, 2011
APA
Kuphal, S., & Kuphal, S. (2011). Phosphorylation of β-catenin results in lack of β-catenin signaling in melanoma. International Journal of Oncology, 39, 235-243. https://doi.org/10.3892/ijo.2011.1028
MLA
Kuphal, S., Bosserhoff, A. K."Phosphorylation of β-catenin results in lack of β-catenin signaling in melanoma". International Journal of Oncology 39.1 (2011): 235-243.
Chicago
Kuphal, S., Bosserhoff, A. K."Phosphorylation of β-catenin results in lack of β-catenin signaling in melanoma". International Journal of Oncology 39, no. 1 (2011): 235-243. https://doi.org/10.3892/ijo.2011.1028