Type VII collagen is required for Ras-driven human epidermal tumorigenesis (Science, 307:1773-1776, 18 March 2005)

報告日期: 2005/11/04
報告時間: 16:00/16:50
報告學生: 鄭舒文
講評老師: 呂增宏
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Type VII Collagen Is Required for Ras-Driven Human Epidermal Tumorigenesis

                SCIENCE, VOL 307, 18 MARCH, 2005.

Speaker : 鄭舒文             Time : Nov 4, 2005(4:00~4:50)

Commentator : 呂增宏  老師         Place : Classroom 602

Abstract:

Early-onset, invasive human squamous cell carcinomas (SCCs )

characterize recessive dystrophic epidermolysis bullosa (RDEB), a blistering skin disorder caused by mutations in the COL7A1 gene that encodes the keratinocyte-secreted type VII collagen epidermal basement membrane zone (BMZ) protein. The major structural component of the collagen VII is anchoring fibrils which is a homotrimer of threeα1(VII) chains, extend from the lamina densa of the epidermal basement membrane into the underlying dermal connective tissue. In order to study the function of collagen VII, authors used the Ras-IkBa which coexpressing in the primary RDEBNull keratinocytes. It can restore tumor formation to RDEBNull  keratinocytes in a non-cell-autonomous manner. Fibronectin -like sequences within NC1 (FNC1) promoted tumor cell invasion in a laminin 5–dependent manner and were also required for tumorigenesis. Antibodies to FNC1, but not NC1, blocked enhanced invasion of normal cells coexpressing Ras and IkBa and that invasiveness of RDEBNull cells was restored by FNC1. Therefore, FNC1 would be accessible to therapeutics such as humanized mAbs.

Reference :

1. Leena Pulkkinen, Jouni UittoU. Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix Biology 18(1999), 29-42.

2. Maya Dajee, Paul A. Khavari. NF-kB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. NATURE, Vol 421 (2003), 639-643.