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β-Catenin Expression and Activation in Conjunctival Melanoma
Emerentienne Larivé1, Michael Nicolas2, Gürkan Kaya3
1Lausanne University, Lausanne, Switzerland.
Dermatopathology (Basel, Switzerland)
|November 9, 2019
Summary
The Wnt pathway, specifically beta-catenin activation, plays a limited role in conjunctival melanoma progression. In vitro studies showed Wnt3a or Wnt5a did not induce nuclear beta-catenin localization in melanoma cells.
Area of Science:
- Ophthalmology
- Oncology
- Molecular Biology
Background:
- Conjunctival melanoma is a rare malignancy.
- The Wnt signaling pathway is implicated in various cancers, including melanoma.
- Beta-catenin is a key mediator of the canonical Wnt pathway.
Purpose of the Study:
- To investigate the role of the canonical Wnt pathway, through beta-catenin activation, in the progression of conjunctival melanoma.
- To evaluate beta-catenin expression in conjunctival nevi, primary acquired melanoses (PAM), and conjunctival melanomas.
Main Methods:
- Immunohistochemistry was used to assess beta-catenin localization in 43 conjunctival nevi, 48 PAM, and 44 conjunctival melanomas.
- In vitro experiments involved stimulating 4 conjunctival melanoma cell lines and 1 skin melanoma cell line with Wnt3a or Wnt5a.
- Wound healing assays were conducted to assess cell motility after Wnt5a stimulation.
Main Results:
- Nuclear beta-catenin expression was observed in 16% of nevi, 15% of melanomas, and 4% of PAM.
- Membranous beta-catenin expression was present in nearly all samples.
- In vitro, Wnt3a or Wnt5a stimulation did not induce nuclear beta-catenin translocation or increase cell motility.
Conclusions:
- Nuclear beta-catenin localization and activation appear limited in conjunctival melanoma.
- The findings suggest that targeting ARF6 for beta-catenin inhibition may not be a viable treatment strategy for conjunctival melanoma.
- Canonical and noncanonical Wnt pathway activation did not significantly impact beta-catenin localization in conjunctival melanoma cells in vitro.
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