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REGγ accelerates melanoma formation by regulating Wnt/β-catenin signalling pathway
Hui Chen1, Xiao Gao1, Zhengwang Sun2
1Shanghai Key Laboratory of regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.
Experimental Dermatology
|June 13, 2017
Summary
The proteasome activator REGγ drives melanoma growth by activating the Wnt/β-catenin pathway. Inhibiting REGγ halts melanoma cell proliferation and tumor growth, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The proteasome activator REGγ is implicated in various cancer pathways.
- The specific role and mechanisms of REGγ in melanoma development are not well understood.
Purpose of the Study:
- To investigate the impact of REGγ on human melanoma cell proliferation in vitro and in vivo.
- To elucidate the molecular mechanisms by which REGγ influences melanoma progression.
Main Methods:
- REGγ was knocked down in human melanoma cell lines and mouse models.
- Melanoma cell proliferation, cell cycle, and xenograft growth were assessed.
- The Wnt/β-catenin signaling pathway, including GSK-3β degradation and β-catenin levels, was analyzed.
- REGγ and β-catenin expression was evaluated in human melanoma samples.
Main Results:
- Knockdown of REGγ significantly inhibited melanoma cell growth and induced G1 phase arrest.
- REGγ depletion suppressed xenograft tumor growth in vivo.
- REGγ was found to activate the Wnt/β-catenin pathway by degrading GSK-3β.
- Inhibition of β-catenin blocked cell proliferation in REGγ-expressing melanoma cells.
- Human melanoma samples showed overexpression of REGγ, correlating positively with β-catenin levels.
Conclusions:
- REGγ is a key regulator in melanoma development, primarily through the Wnt/β-catenin signaling pathway.
- Targeting REGγ presents a potential therapeutic strategy for melanoma treatment.
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