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Links between α-catenin, NF-κB, and squamous cell carcinoma in skin

2006; National Academy of Sciences; Volume: 103; Issue: 7 Linguagem: Inglês

10.1073/pnas.0510422103

1091-6490

Agnieszka Kobielak, Elaine Fuchs,

NF-κB Signaling Pathways

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, α-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 α-catenin ablation is accompanied by activation of NF-κB 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 α-catenin. We show that reductions in α-catenin, activation of NF-κB, and inflammation are common features of human squamous cell carcinomas of the skin.