WNT1-inducible-signaling pathway protein 3 explained

WNT1-inducible-signaling pathway protein 3^{[1] [2]} (WISP3, also named CCN6) is a matricellular protein that in humans is encoded by the WISP3 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 CYR61 (cysteine-rich angiogenic inducer 61, or CCN1), 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 (IGFBP), von Willebrand type C repeats (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.^{[3] [4] [5]}

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.^[6] However, mice with WISP3 knockout or overexpression are normal and suffer no apparent developmental defect.^{[7] [8]} 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.^[2]

Notes and References

1. Jun JI, Lau LF . Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets . Nat Rev Drug Discov . 10 . 12 . 945–63 . December 2011 . 22129992 . 10.1038/nrd3599 . 3663145 .
2. Huang W, Pal A, Kleer CG . On how CCN6 suppresses breast cancer growth and invasion . J Cell Commun Signal . 6 . 1 . 5–10 . March 2012 . 21842227 . 3271195 . 10.1007/s12079-011-0148-9 .
3. Chen CC, Lau LF . Functions and mechanisms of action of CCN matricellular proteins . Int. J. Biochem. Cell Biol. . 41 . 4 . 771–83 . April 2009 . 18775791 . 2668982 . 10.1016/j.biocel.2008.07.025 .
4. Holbourn KP, Acharya KR, Perbal B . The CCN family of proteins: structure-function relationships . Trends Biochem. Sci. . 33 . 10 . 461–73 . October 2008 . 18789696 . 2683937 . 10.1016/j.tibs.2008.07.006 .
5. Leask A, Abraham DJ . All in the CCN family: essential matricellular signaling modulators emerge from the bunker . J. Cell Sci. . 119 . Pt 23 . 4803–10 . December 2006 . 17130294 . 10.1242/jcs.03270 . free .
6. 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 . Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia . Nat. Genet. . 23 . 1 . 94–8 . September 1999 . 10471507 . 10.1038/12699 . 31389994 .
7. Kutz WE, Gong Y, Warman ML . WISP3, the gene responsible for the human skeletal disease progressive pseudorheumatoid dysplasia, is not essential for skeletal function in mice . Mol. Cell. Biol. . 25 . 1 . 414–21 . January 2005 . 15601861 . 538768 . 10.1128/MCB.25.1.414-421.2005 .
8. Nakamura Y, Cui Y, Fernando C, Kutz WE, Warman ML . Normal growth and development in mice over-expressing the CCN family member WISP3 . J Cell Commun Signal . 3 . 2 . 105–13 . June 2009 . 19401829 . 2721080 . 10.1007/s12079-009-0040-z .