期刊
MOLECULAR CANCER RESEARCH
卷 12, 期 9, 页码 1244-1253出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-14-0223-T
关键词
-
资金
- Intramural Research Program of the NIH
- NCI
- Center for Cancer Research
Wnt signaling is critical to maintaining cellular homeostasis via regulation of cell division, mitigation of cell stress, and degradation. Aberrations in Wnt signaling contribute to carcinogenesis and metastasis, whereas sirtuins have purported roles in carcinogenesis, aging, and neurodegeneration. Therefore, the hypothesis that sirtuin 2 (SIRT2) directly interacts with beta-catenin and whether this interaction alters the expression of Wnt target genes to produce an altered cellular phenotype was tested. Coimmunoprecipitation studies, using mouse embryonic fibroblasts (MEF) from Sirt2 wild-type and genomic knockout mice, demonstrate that beta-catenin directly binds SIRT2. Moreover, this interaction increases in response to oxidative stress induced by ionizing radiation. In addition, this association inhibits the expression of important Wnt target genes such as survivin (BIRC5), cyclin D1 (CCND1), and c-myc (MYC). In Sirt2 null MEFs, an upregulation of matrix metalloproteinase 9 (MMP9) and decreased E-cadherin (CDH1) expression is observed that produces increased cellular migration and invasion. Together, these data demonstrate that SIRT2, a tumor suppressor lost in multiple cancers, inhibits the Wnt signaling pathway in nonmalignant cells by binding to beta-catenin and that SIRT2 plays a critical role in the response to oxidative stress from radiation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据