Role of Wnt Signaling in melanoma metastasis and melanocyte differentiation

Wnt 信号转导在黑色素瘤转移和黑色素细胞分化中的作用

• 批准号: 7963979
• 负责人: Ashani Weeraratna
• 金额: $ 25.14万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7963979
• 关键词: Affect; Cytoskeleton; Data; Differentiation Antigens; Down-Regulation; Goals; Heparan Sulfate Proteoglycan; Maintenance; Malignant Neoplasms; Melanoma Cell; Neoplasm Metastasis; Orphan; Phenotype; Pigments; Population; Process; RORA gene; Receptor Protein-Tyrosine Kinases; Research; Role; Signal Transduction; Stem cells; Wnt proteins; cancer stem cell; epithelial to mesenchymal transition; immunogenicity; melanocyte; melanoma; neoplastic cell; self renewing cell; syndecan-4; tumor

We have shown that Wnt5A is a molecule that is important in the progression of melanoma cells to a highly metastatic state. Recently we have demonstrated that Wnt5A acts via the orphan tyrosine kinase receptor, ROR2, and that this interaction is modulated by heparan sulfate proteoglycans such as syndecan 4. The signaling of Wnt5A involves changes in the cytoskeleton, activation of an epithelial to mesenchymal transition and the loss of immunogenicity via the downregulation of melanocyte differentiation antigens and pigment. These features are consistent with a de-differentiation phenotype of melanoma cells. Given recent data that suggested that the Wnt protein, Wnt5A, can affect the proliferation and maintenance of hemaopoietic stem cells, we are trying to determine what the role, if any, of Wnt5A in the maintenance and profileration of the melanoma stem cell might be, and how this relates to the role of Wnt5A in melanoma metastasis.

我们已经表明，Wnt5a是一种在黑色素瘤细胞向高度转移态的进展中很重要的分子。最近，我们已经证明Wnt5a通过孤立酪氨酸激酶受体ROR2起作用，并且这种相互作用是由硫酸乙酰肝素蛋白聚糖（如syndecan 4）调节的。Wnt5a的信号涉及细胞骨架的激活，弥漫到脉络膜损失的激活和损失的变化。抗原和色素。 这些特征与黑色素瘤细胞的去分化表型一致。鉴于最近的数据表明Wnt蛋白Wnt5a会影响血型干细胞的增殖和维持，我们正在尝试确定Wnt5a在黑色素瘤干细胞的维持和可能性中的作用（如果有的话）可能是什么，以及与黑色素瘤中Wnt5a的作用如何相关。