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PMID: 16452166 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Links between alpha-catenin, NF-kappaB, and squamous cell carcinoma in skin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 7 ·2006-02-14 ·Pages 2322-7

Kobielak A, Fuchs E

Abstract

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.

MeSH Terms
Animals Carcinoma, Squamous Cell/chemistry,genetics,pathology Cell Proliferation Cell Transformation, Neoplastic/genetics,pathology Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Inflammation/genetics Mice Mice, Knockout Mutation NF-kappa B/analysis,genetics Neoplasm Invasiveness Neovascularization, Physiologic/genetics Oligonucleotide Array Sequence Analysis Signal Transduction Skin Neoplasms/chemistry,genetics,pathology Up-Regulation Wound Healing/genetics alpha Catenin/analysis,genetics
Chemicals
NF-kappa B alpha Catenin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kobielak Agnieszka
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021, USA.
Fuchs Elaine
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0510422103
Published
2006-02-14
Epub
2006-00-01
Pages
2322-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1413714
Subset
IM
Grants
NIAMS NIH HHS · R01 AR027883 · United States
NIAMS NIH HHS · R37 AR027883 · United States
NIAMS NIH HHS · AR27883 · United States
External Links
PubMed source DOI: 10.1073/pnas.0510422103 PMC Full Text View journal details
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