Links between alpha-catenin, NF-kappaB, and squamous cell carcinoma in skin.
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-kappaB 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-kappaB, and inflammation are common features of human squamous cell carcinomas of the skin.
Kobielak
Agnieszka
A
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021, USA.
Fuchs
Elaine
E
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics*; D009361:Neoplasm Invasiveness; D018919:Neovascularization, Physiologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics; D051178:alpha Catenin / Q000032:analysis / Q000235:genetics*
D016328:NF-kappa B; D051178:alpha Catenin