'''WNT1-inducible-signaling pathway protein 2''', or WISP-2 (also named CCN5) is a [[matricellular protein]] that in humans is encoded by the ''WISP2'' [[gene]].<ref>{{cite journal | vauthors = Jun JI, Lau LF | title = Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets | journal = Nature Reviews. Drug Discovery | volume = 10 | issue = 12 | pages = 945–63 | date = Dec 2011 | pmid = 22129992 | doi = 10.1038/nrd3599 }}</ref><ref>{{cite journal | vauthors = Russo JW, Castellot JJ | title = CCN5: biology and pathophysiology | journal = Journal of Cell Communication and Signaling | volume = 4 | issue = 3 | pages = 119–30 | date = Oct 2010 | pmid = 21063502 | pmc = 2948116 | doi = 10.1007/s12079-010-0098-7 }}</ref>
'''WNT1-inducible-signaling pathway protein 2''', or WISP-2 (also named CCN5) is a [[matricellular protein]] that in humans is encoded by the ''WISP2'' [[gene]].<ref>{{cite journal | vauthors = Jun JI, Lau LF | title = Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets | journal = Nature Reviews. Drug Discovery | volume = 10 | issue = 12 | pages = 945–63 | date = Dec 2011 | pmid = 22129992 | doi = 10.1038/nrd3599 | pmc = 3663145 }}</ref><ref>{{cite journal | vauthors = Russo JW, Castellot JJ | title = CCN5: biology and pathophysiology | journal = Journal of Cell Communication and Signaling | volume = 4 | issue = 3 | pages = 119–30 | date = Oct 2010 | pmid = 21063502 | pmc = 2948116 | doi = 10.1007/s12079-010-0098-7 }}</ref>
WISP-2 is a member of the CCN family (CCN intercellular signaling protein) of secreted, extracellular matrix (ECM)-associated signaling matricellular proteins. The CCN acronym is derived from the first three members of the family identified, namely CYR61 (CCN1), CTGF (connective tissue growth factor, or CCN2), and NOV. These proteins, together with WISP1/CCN4, WISP2 (CCN5, this gene), and WISP3 (CCN6) comprise the six-member CCN family in vertebrates. CCN proteins characteristically contain an N-terminal secretory signal peptide followed by four structurally 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. However, WISP-2 is unique among this family of proteins by lacking precisely the CT domain.
Clinical significance
WISP-2 (CCN5) inhibits the proliferation of vascular smooth muscle cells,[6] human uterine myometrial cells, and leiomyoma cells.[7] Ectopic expression of WISP-2 also inhibits the motility and invasiveness of breast carcinoma cells.[8][9] WISP-2 also inhibits cardiac hypertrophy and fibrosis, an effect that appears linked to the absence of the CT domain.[10]
↑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.
↑Mason HR, Lake AC, Wubben JE, Nowak RA, Castellot JJ (Mar 2004). "The growth arrest-specific gene CCN5 is deficient in human leiomyomas and inhibits the proliferation and motility of cultured human uterine smooth muscle cells". Molecular Human Reproduction. 10 (3): 181–7. doi:10.1093/molehr/gah028. PMID14981145.
↑Banerjee S, Dhar G, Haque I, Kambhampati S, Mehta S, Sengupta K, Tawfik O, Phillips TA, Banerjee SK (Sep 2008). "CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression of the disease and suppresses the invasive phenotypes of tumor cells". Cancer Research. 68 (18): 7606–12. doi:10.1158/0008-5472.CAN-08-1461. PMID18794149.
↑Yoon PO, Lee MA, Cha H, Jeong MH, Kim J, Jang SP, Choi BY, Jeong D, Yang DK, Hajjar RJ, Park WJ (Aug 2010). "The opposing effects of CCN2 and CCN5 on the development of cardiac hypertrophy and fibrosis". Journal of Molecular and Cellular Cardiology. 49 (2): 294–303. doi:10.1016/j.yjmcc.2010.04.010. PMID20430035.
