Abstract
Type XIX collagen is a minor collagen associated with basement membranes. It was isolated for the first time in a human cDNA library from rhabdomyosarcoma and belongs to the FACITs family (Fibril Associated Collagens with Interrupted Triple Helices). Previously, we demonstrated that the NC1 domain of collagen XIX (NC1(XIX)) exerts anti-tumor properties on melanoma cells by inhibiting their migration and invasion. In the present work, we identified for the first time the integrin αvβ3 as a receptor of NC1(XIX). Moreover, we demonstrated that NC1(XIX) inhibits the FAK/PI3K/Akt/mTOR pathway, by decreasing the phosphorylation and activity of the major proteins involved in this pathway. On the other hand, NC1(XIX) induced an increase of GSK3β activity by decreasing its degree of phosphorylation. Treatments targeting this central signaling pathway in the development of melanoma are promising and new molecules should be developed. NC1(XIX) seems to have the potential for the design of new anti-cancer drugs.
Highlights
Collagen XIX was isolated from human rhabdomyosarcoma cells in 1992 by Hidei Yoshioka, under the name of collagen Y [1]
We showed that plasmin, a key enzyme in tumor invasion, releases a peptide derived from the NC1 domain that has the same anti-tumor effects as the entire NC1 domain [9]
Our previous studies demonstrated that the NC1 domain of collagen XIX had anti-tumor effects by inhibiting migration and invasion of melanoma cells without affecting their proliferation [15, 16]
Summary
Collagen XIX was isolated from human rhabdomyosarcoma cells in 1992 by Hidei Yoshioka, under the name of collagen Y [1]. According to its amino acid sequence, it was classified in the FACIT family (Fibril Associated Collagens with Interrupted Triple helices). This initial classification was confirmed by several groups [2, 3]. The type XIX collagen is a homotrimer of 400 kDa, composed of the combination of three 112 kDa α1(XIX) chains. Unlike other FACIT collagens, α1(XIX) collagen chain has interchain and intrachain disulfide bonds which allow the formation of oligomers of different sizes [5, 8]. We have recently shown in the laboratory that the 19 amino acid NC1(XIX) forms intrachain disulfide bonds in solution [9]
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