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.
WISP-2 (CCN5) inhibits the proliferation of vascular smooth muscle cells,[10] human uterine myometrial cells, and leiomyoma cells.[11] Ectopic expression of WISP-2 also inhibits the motility and invasiveness of breast carcinoma cells.[12][13] WISP-2 also inhibits cardiac hypertrophy and fibrosis, an effect that appears linked to the absence of the CT domain.[14]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Jun JI, Lau LF (Dec 2011). "Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets". Nature Reviews. Drug Discovery. 10 (12): 945–63. doi:10.1038/nrd3599. PMC3663145. PMID22129992.945-63&rft.date=2011-12&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663145#id-name=PMC&rft_id=info:pmid/22129992&rft_id=info:doi/10.1038/nrd3599&rft.aulast=Jun&rft.aufirst=JI&rft.au=Lau, LF&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663145&rfr_id=info:sid/en.wikipedia.org:WNT1-inducible-signaling pathway protein 2" class="Z3988">
^Russo JW, Castellot JJ (Oct 2010). "CCN5: biology and pathophysiology". Journal of Cell Communication and Signaling. 4 (3): 119–30. doi:10.1007/s12079-010-0098-7. PMC2948116. PMID21063502.119-30&rft.date=2010-10&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948116#id-name=PMC&rft_id=info:pmid/21063502&rft_id=info:doi/10.1007/s12079-010-0098-7&rft.aulast=Russo&rft.aufirst=JW&rft.au=Castellot, JJ&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948116&rfr_id=info:sid/en.wikipedia.org:WNT1-inducible-signaling pathway protein 2" class="Z3988">
^Chen CC, Lau LF (Apr 2009). "Functions and mechanisms of action of CCN matricellular proteins". The International Journal of Biochemistry & Cell Biology. 41 (4): 771–83. doi:10.1016/j.biocel.2008.07.025. PMC2668982. PMID18775791.771-83&rft.date=2009-04&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668982#id-name=PMC&rft_id=info:pmid/18775791&rft_id=info:doi/10.1016/j.biocel.2008.07.025&rft.aulast=Chen&rft.aufirst=CC&rft.au=Lau, LF&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668982&rfr_id=info:sid/en.wikipedia.org:WNT1-inducible-signaling pathway protein 2" class="Z3988">
^Holbourn KP, Acharya KR, Perbal B (Oct 2008). "The CCN family of proteins: structure-function relationships". Trends in Biochemical Sciences. 33 (10): 461–73. doi:10.1016/j.tibs.2008.07.006. PMC2683937. PMID18789696.461-73&rft.date=2008-10&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683937#id-name=PMC&rft_id=info:pmid/18789696&rft_id=info:doi/10.1016/j.tibs.2008.07.006&rft.aulast=Holbourn&rft.aufirst=KP&rft.au=Acharya, KR&rft.au=Perbal, B&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683937&rfr_id=info:sid/en.wikipedia.org:WNT1-inducible-signaling pathway protein 2" class="Z3988">
^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. S2CID334940.4803-10&rft.date=2006-12&rft_id=https://api.semanticscholar.org/CorpusID:334940#id-name=S2CID&rft_id=info:pmid/17130294&rft_id=info:doi/10.1242/jcs.03270&rft.aulast=Leask&rft.aufirst=A&rft.au=Abraham, DJ&rfr_id=info:sid/en.wikipedia.org:WNT1-inducible-signaling pathway protein 2" class="Z3988">
^Lake AC, Bialik A, Walsh K, Castellot JJ (Jan 2003). "CCN5 is a growth arrest-specific gene that regulates smooth muscle cell proliferation and motility". The American Journal of Pathology. 162 (1): 219–31. doi:10.1016/S0002-9440(10)63813-8. PMC1851113. PMID12507905.219-31&rft.date=2003-01&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851113#id-name=PMC&rft_id=info:pmid/12507905&rft_id=info:doi/10.1016/S0002-9440(10)63813-8&rft.aulast=Lake&rft.aufirst=AC&rft.au=Bialik, A&rft.au=Walsh, K&rft.au=Castellot, JJ&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851113&rfr_id=info:sid/en.wikipedia.org:WNT1-inducible-signaling pathway protein 2" class="Z3988">
^Fritah A, Saucier C, De Wever O, Bracke M, Bièche I, Lidereau R, Gespach C, Drouot S, Redeuilh G, Sabbah M (Feb 2008). "Role of WISP-2/CCN5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells". Molecular and Cellular Biology. 28 (3): 1114–23. doi:10.1128/MCB.01335-07. PMC2223394. PMID18070926.1114-23&rft.date=2008-02&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223394#id-name=PMC&rft_id=info:pmid/18070926&rft_id=info:doi/10.1128/MCB.01335-07&rft.aulast=Fritah&rft.aufirst=A&rft.au=Saucier, C&rft.au=De Wever, O&rft.au=Bracke, M&rft.au=Bièche, I&rft.au=Lidereau, R&rft.au=Gespach, C&rft.au=Drouot, S&rft.au=Redeuilh, G&rft.au=Sabbah, M&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223394&rfr_id=info:sid/en.wikipedia.org:WNT1-inducible-signaling pathway protein 2" class="Z3988">
^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. PMID20430035.294-303&rft.date=2010-08&rft_id=info:doi/10.1016/j.yjmcc.2010.04.010&rft_id=info:pmid/20430035&rft.aulast=Yoon&rft.aufirst=PO&rft.au=Lee, MA&rft.au=Cha, H&rft.au=Jeong, MH&rft.au=Kim, J&rft.au=Jang, SP&rft.au=Choi, BY&rft.au=Jeong, D&rft.au=Yang, DK&rft.au=Hajjar, RJ&rft.au=Park, WJ&rfr_id=info:sid/en.wikipedia.org:WNT1-inducible-signaling pathway protein 2" class="Z3988">