Links between α-catenin, NF-κB, and squamous cell carcinoma in skin
Links between α-catenin, NF-κB, and squamous cell carcinoma in skin
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DOI：
10.1073/pnas.0510422103
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发表时间：
2006-02-14
影响因子：
11.1
通讯作者：
Fuchs, E
中科院分区：
文献类型：
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作者：
Kobielak, A;Fuchs, E
癌症表现出多种细胞缺陷，这些缺陷被认为是由多种基因突变引起的。在这项研究中，我们发现，当一个单一的粘附连接蛋白，α -连环蛋白，被条件靶向去除时，整个皮肤表皮系统地转变为一个充满炎症的超增殖侵入性组织。转录谱分析和生化分析显示，α -连环蛋白消融伴随着NF-kappa B及其促炎靶基因的激活，以及参与增殖、伤口愈合、血管生成和转移的基因的激活。许多这些改变发生在体外和胚胎中，因此似乎至少部分与α -连环蛋白的缺失有关。我们发现，α -连环蛋白的减少，nf - κ B的激活和炎症是人类皮肤鳞状细胞癌的共同特征。
Cancers display a diverse set of cellular defects, which are thought to be elicited by multiple genetic mutations. In this study, we show that when a single adherens junction protein, alpha-catenin, is removed by conditional targeting, the entire skin epidermis systematically transforms to a hyperproliferative, invasive tissue replete with inflammation. Transcriptional profiling and biochemical analyses reveal that alpha-catenin ablation is accompanied by activation of NF-kappa B and its proinflammatory target genes, along with genes involved in proliferation, wound healing, angiogenesis, and metastasis. Many of these alterations occur in vitro and in the embryo, and thus seem at least partly to be intrinsic to the loss of alpha-catenin. We show that reductions in alpha-catenin, activation of NF-kappa B, and inflammation are common features of human squamous cell carcinomas of the skin.