BMB Reports 2018; 51(10): 486-492
Role of the CCN protein family in cancer
Hyungjoo Kim1, Seogho Son1 and Incheol Shin1,2,*
1Department of Life Science, Hanyang University, Seoul 04763, 2Natural Science Institute, Hanyang University, Seoul 04763, Korea
Correspondence to: Tel: +82-2-2220-2562; Fax: +82-2-2298-2562; E-mail:
Received: July 20, 2018; Published online: October 31, 2018.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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The CCN protein family is composed of six matricellular proteins, which serve regulatory roles rather than structural roles in the extracellular matrix. First identified as secreted proteins which are induced by oncogenes, the acronym CCN came from the names of the first three members: CYR61, CTGF, and NOV. All six members of the CCN family consist of four cysteine-rich modular domains. CCN proteins are known to regulate cell adhesion, proliferation, differentiation, and apoptosis. In addition, CCN proteins are associated with cardiovascular and skeletal development, injury repair, inflammation, and cancer. They function either through binding to integrin receptors or by regulating the expression and activity of growth factors and cytokines. Given their diverse roles related to the pathology of certain diseases such as fibrosis, arthritis, atherosclerosis, diabetic nephropathy, retinopathy, and cancer, there are many emerging studies targeting CCN protein signaling pathways in attempts to elucidate their potentials as therapeutic targets.
Keywords: Cancer, CCN family, Matricellular protein, Signal transduction, Therapeutic target
Fig. 1. Structure and nomenclature of CCN protein family members. (Left) The amino acid location of the four conserved motifs (IGFBP, VWC, TSR, and CT) are represented as Arabic numerals. (Right) Alternative names for the CCN proteins are indicated. Abbreviations: Cyr61, cysteine rich 61; CTGF-2, connective tissue growth factor 2; IGFBP10, insulin-like growth factor-binding protein 10; IGFBP-rP4, IGFBP-related protein 4; HBGF-0.8, heparin-binding growth factor 0.8; HCS24, hypertrophic chondrocyte specific 24; NOV, nephroblastoma overexpressed gene; NOVH, human nov gene; Wisp, Wnt-inducible secreted protein; Elm-1, expressed in low metastatic cells; HICP, heparin-induced CCN-like protein; and Cop-1, card-only protein 1.

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