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

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.
AuthorsSilke Kuphal, Anja Katrin Bosserhoff
JournalInternational journal of oncology (Int J Oncol) Vol. 39 Issue 1 Pg. 235-43 (Jul 2011) ISSN: 1791-2423 [Electronic] Greece
PMID21584489 (Publication Type: Journal Article)
Chemical References
  • beta Catenin
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Space (metabolism)
  • Melanoma (physiopathology)
  • Phosphorylation (genetics)
  • Protein Transport
  • Signal Transduction
  • Transcription, Genetic
  • beta Catenin (genetics, metabolism)

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