Publication Date:
2005-03-19
Description:
Type VII collagen defects cause recessive dystrophic epidermolysis bullosa (RDEB), a blistering skin disorder often accompanied by epidermal cancers. To study the role of collagen VII in these cancers, we examined Ras-driven tumorigenesis in RDEB keratinocytes. Cells devoid of collagen VII did not form tumors in mice, whereas those retaining a specific collagen VII fragment (the amino-terminal noncollagenous domain NC1) were tumorigenic. Forced NC1 expression restored tumorigenicity to collagen VII-null epidermis in a non-cell-autonomous fashion. Fibronectin-like sequences within NC1 (FNC1) promoted tumor cell invasion in a laminin 5-dependent manner and were required for tumorigenesis. Tumor-stroma interactions mediated by collagen VII thus promote neoplasia, and retention of NC1 sequences in a subset of RDEB patients may contribute to their increased susceptibility to squamous cell carcinoma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ortiz-Urda, Susana -- Garcia, John -- Green, Cheryl L -- Chen, Lei -- Lin, Qun -- Veitch, Dallas P -- Sakai, Lynn Y -- Lee, Hyangkyu -- Marinkovich, M Peter -- Khavari, Paul A -- AR43799/AR/NIAMS NIH HHS/ -- AR44012/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Mar 18;307(5716):1773-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉VA Palo Alto Healthcare System, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15774758" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Adult
;
Animals
;
Antibodies/immunology
;
Apoptosis
;
Carcinoma, Squamous Cell/etiology/*physiopathology
;
Cell Adhesion Molecules/immunology/metabolism
;
Cell Proliferation
;
Cell Transformation, Neoplastic
;
Child
;
Collagen Type VII/chemistry/*genetics/immunology/*physiology
;
Disease Susceptibility
;
Epidermolysis Bullosa Dystrophica/complications/*genetics/metabolism/pathology
;
Female
;
*Genes, ras
;
Humans
;
I-kappa B Proteins/genetics/metabolism
;
Keratinocytes/*metabolism/pathology
;
Male
;
Mice
;
Mice, SCID
;
Middle Aged
;
Mutation
;
Neoplasm Invasiveness
;
Protein Structure, Tertiary
;
Skin Neoplasms/etiology/pathology/*physiopathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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