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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Menin represses malignant phenotypes of melanoma through regulating multiple pathways
Shu-Bin Gao1, Zi-Jie Feng, Bin Xu
1Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, China.
Journal of Cellular and Molecular Medicine
|December 7, 2010
Summary
The MEN1 gene product, menin, suppresses melanoma cell growth and migration. Reduced menin expression, linked to promoter hypermethylation, may drive melanoma progression by altering PTN signaling pathways.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Chromosome 11q is implicated in melanoma development.
- Mutations in the MEN1 gene cause Multiple Endocrine Neoplasia type 1 (MEN1) syndrome.
- MEN1 patients exhibit increased risk for malignant melanoma, but the underlying mechanisms are unclear.
Purpose of the Study:
- To investigate the role of the MEN1 gene and its product, menin, in melanoma.
- To elucidate the molecular pathways through which menin influences melanoma phenotypes.
- To explore the epigenetic regulation of MEN1 in melanoma cells.
Main Methods:
- Ectopic expression of menin in melanoma cells.
- In vitro and in vivo assays for cell proliferation and migration.
- Analysis of signaling pathways including PTN, RPTPβ/ζ, PI3K, FAK, and ERK1/2.
- Investigation of MEN1 promoter methylation status.
Main Results:
- Ectopic menin expression inhibited melanoma cell proliferation and migration.
- Menin suppressed the expression of pleiotrophin (PTN) and receptor protein tyrosine phosphatase (RPTP) β/ζ.
- Menin reduced phosphatidylinositol 3-kinase (PI3K) expression and phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK1/2).
- Reduced menin expression in melanoma cells correlated with MEN1 promoter hypermethylation.
Conclusions:
- Menin functions as a tumor suppressor in melanoma by inhibiting malignant phenotypes.
- Menin regulates melanoma progression through modulation of PTN signaling.
- Epigenetic silencing of the MEN1 gene via promoter hypermethylation contributes to melanoma development.
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