WNT1-inducible-signaling pathway protein 1 (WISP-1),[1] also known as CCN4, is a matricellular protein that in humans is encoded by the WISP1gene.[2][3]
WISP-1 is highly homologous to CYR61 (CCN1) and CTGF (CCN2), and is a member of the CCN family of secreted, extracellular matrix (ECM)-associated signaling proteins (CCN intercellular signaling protein). The CCN family of proteins shares a common molecular protein structure, characterized by an N-terminal secretory signal peptide followed by four distinct domains with homologies to insulin-like growth factor binding protein (IGFBP), von Willebrand type C repeats (vWC), thrombospondin type 1 repeat (TSR), and a cysteine knot motif within the C-terminal (CT) domain. This family of proteins regulates diverse cellular functions, including cell adhesion, migration, proliferation, differentiation, and survival.[1][4][5][6]
Role in bone development
WISP-1 promotes mesenchymal cell proliferation and osteoblastic differentiation, and represses chondrocytic differentiation.[7] WISP-1 binds BMP2 and enhances BMP2 function in osteogenesis.[8] These activities may be modulated by its direct binding to decorin and biglycan,[9] two members of a family of small leucine-rich proteoglycans present in the extracellular matrix of connective tissue.
Clinical significance
WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase,[10] and inhibits TNF-induced cell death in cardiomyocytes.[11] Recombinant WISP-1 enhances ECM deposition in human fibroblasts, suggesting that it might play a role in matrix remodeling in vivo. WISP-1 is upregulated in human patients with idiopathicpulmonary fibrosis and in a mouse model of bleomycin-induced lung fibrosis.[12] Orotracheal application of WISP-1 neutralizing antibodies to the lung ameliorates bleomycin-induced lung fibrosis,[12] raising the possibility that WISP-1 might be a potential target for anti-fibrotic therapy.[1]
Expression of WISP-1 promotes tumor growth,[13] and high WISP-1 expression correlates with advanced tumors of the brain, breast, colon, and lung.[14][15][16][17] WISP-1 appears to inhibit metastasis[18][19] although expression of a WISP-1 splicing variant lacking the VWC domain appears to enhance the invasive characteristic of gastric carcinoma cells.[20]
↑Leask A, Abraham DJ (Dec 2006). "All in the CCN family: essential matricellular signaling modulators emerge from the bunker". Journal of Cell Science. 119 (Pt 23): 4803–10. doi:10.1242/jcs.03270. PMID17130294.
↑Desnoyers L, Arnott D, Pennica D (Dec 2001). "WISP-1 binds to decorin and biglycan". The Journal of Biological Chemistry. 276 (50): 47599–607. doi:10.1074/jbc.M108339200. PMID11598131.
↑Kim Y, Kim KH, Lee J, Lee YA, Kim M, Lee SJ, Park K, Yang H, Jin J, Joo KM, Lee J, Nam DH (Mar 2012). "Wnt activation is implicated in glioblastoma radioresistance". Laboratory Investigation. 92 (3): 466–73. doi:10.1038/labinvest.2011.161. PMID22083670.
↑Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP (Dec 2001). "Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features". Cancer Research. 61 (24): 8917–23. PMID11751417.
↑Tian C, Zhou ZG, Meng WJ, Sun XF, Yu YY, Li L, Luo HZ, Yang L, Zhou B, Gu J (Jul 2007). "Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients". World Journal of Gastroenterology. 13 (28): 3878–82. doi:10.3748/wjg.v13.i28.3878. PMID17657846.
↑Soon LL, Yie TA, Shvarts A, Levine AJ, Su F, Tchou-Wong KM (Mar 2003). "Overexpression of WISP-1 down-regulated motility and invasion of lung cancer cells through inhibition of Rac activation". The Journal of Biological Chemistry. 278 (13): 11465–70. doi:10.1074/jbc.M210945200. PMID12529380.
↑Tanaka S, Sugimachi K, Saeki H, Kinoshita J, Ohga T, Shimada M, Maehara Y, Sugimachi K (Sep 2001). "A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma". Oncogene. 20 (39): 5525–32. doi:10.1038/sj.onc.1204723. PMID11571650.
