科研之友
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摘要
The Wnt/beta-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 beta-catenin activity in this type of skin cancer. Interestingly, localization of beta-catenin protein was basically cytoplasmic in melanomas in vivo, which was in clear contrast to findings in colon carcinoma. Congruently, the transcriptional activity of beta-catenin regulating expression of beta-catenin target genes was not observed in several melanoma cell lines. Further, neither LiC1 nor Wnt agonist treatment led to significant activation of beta-catenin signaling. This lack in functionality seems to depend on phosphorylation at threonine 41 and serine 45 of beta-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 beta-catenin function. This alternative beta-catenin signaling pathway should be considered when thinking about targeting beta-catenin in melanoma treatment.
- 出版日期2011-7
