View source for Biology:WNT1-inducible-signaling pathway protein 3

{{Infobox_gene}}
'''WNT1-inducible-signaling pathway protein 3'''<ref name="pmid22129992">{{cite journal | vauthors = Jun JI, Lau LF | title = Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets | journal = Nat Rev Drug Discov | volume = 10 | issue = 12 | pages = 945–63 |date=December 2011 | pmid = 22129992 | doi = 10.1038/nrd3599 | pmc = 3663145 }}</ref><ref name="ReferenceA">{{cite journal | vauthors = Huang W, Pal A, Kleer CG | title = On how CCN6 suppresses breast cancer growth and invasion | journal = J Cell Commun Signal | volume = 6 | issue = 1 | pages = 5–10 |date=March 2012 | pmid = 21842227 | pmc = 3271195 | doi = 10.1007/s12079-011-0148-9 }}</ref> (WISP3, also named CCN6) is a matricellular protein that in humans is encoded by the ''WISP3'' [[Biology:Gene|gene]].

== Structure ==

It 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 [[Biology:CYR61|CYR61]] (cysteine-rich angiogenic inducer 61, or CCN1), [[Biology:CTGF|CTGF]] (connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3). These proteins, together with WISP1 (CCN4), and WISP2 (CCN5) 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 ([[Biology:Insulin-like growth factor-binding protein|IGFBP]]), von Willebrand type C repeats ([[Biology:Von Willebrand factor type C domain|vWC]]), thrombospondin type 1 repeat (TSR), and a cysteine knot motif within the C-terminal (CT) domain.

== Function ==

The CCN family of proteins regulates diverse cellular functions, including cell adhesion, migration, proliferation, survival, and differentiation.<ref name="pmid18775791">{{cite journal | vauthors = Chen CC, Lau LF | title = Functions and mechanisms of action of CCN matricellular proteins | journal = Int. J. Biochem. Cell Biol. | volume = 41 | issue = 4 | pages = 771–83 |date=April 2009 | pmid = 18775791 | pmc = 2668982 | doi = 10.1016/j.biocel.2008.07.025 }}</ref><ref name="pmid18789696">{{cite journal | vauthors = Holbourn KP, Acharya KR, Perbal B | title = The CCN family of proteins: structure-function relationships | journal = Trends Biochem. Sci. | volume = 33 | issue = 10 | pages = 461–73 |date=October 2008 | pmid = 18789696 | pmc = 2683937 | doi = 10.1016/j.tibs.2008.07.006 }}</ref><ref name="pmid17130294">{{cite journal | vauthors = Leask A, Abraham DJ | title = All in the CCN family: essential matricellular signaling modulators emerge from the bunker | journal = J. Cell Sci. | volume = 119 | issue = Pt 23 | pages = 4803–10 |date=December 2006 | pmid = 17130294 | doi = 10.1242/jcs.03270 | doi-access = free }}</ref>

== Clinical significance ==

Mutations in the human WISP3 gene are associated with progressive pseudorheumatoid dysplasia, a juvenile onset autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis.<ref name="pmid10471507">{{cite journal | vauthors = Hurvitz JR, Suwairi WM, Van Hul W, El-Shanti H, Superti-Furga A, Roudier J, Holderbaum D, Pauli RM, Herd JK, Van Hul EV, Rezai-Delui H, Legius E, Le Merrer M, Al-Alami J, Bahabri SA, Warman ML | title = Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia | journal = Nat. Genet. | volume = 23 | issue = 1 | pages = 94–8 |date=September 1999 | pmid = 10471507 | doi = 10.1038/12699 | s2cid = 31389994 }}</ref> However, mice with WISP3 knockout or overexpression are normal and suffer no apparent developmental defect.<ref name="pmid15601861">{{cite journal | vauthors = Kutz WE, Gong Y, Warman ML | title = WISP3, the gene responsible for the human skeletal disease progressive pseudorheumatoid dysplasia, is not essential for skeletal function in mice | journal = Mol. Cell. Biol. | volume = 25 | issue = 1 | pages = 414–21 |date=January 2005 | pmid = 15601861 | pmc = 538768 | doi = 10.1128/MCB.25.1.414-421.2005 }}</ref><ref name="pmid19401829">{{cite journal | vauthors = Nakamura Y, Cui Y, Fernando C, Kutz WE, Warman ML | title = Normal growth and development in mice over-expressing the CCN family member WISP3 | journal = J Cell Commun Signal | volume = 3 | issue = 2 | pages = 105–13 |date=June 2009 | pmid = 19401829 | pmc = 2721080 | doi = 10.1007/s12079-009-0040-z }}</ref> Loss of WISP3 expression is associated with aggressive inflammatory breast cancer and breast cancer with axillary lymph node metastasis, suggesting that WISP3/CCN6 may function as a suppressor of breast cancer growth and metastasis.<ref name="ReferenceA"/>

==References==
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