Type VII collagen is required for Ras-driven human epidermal tumorigenesis by 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 in Science (New York, N.Y.) (2005).

[PMID: 15774758] PubMed


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.

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