The CCN family proteins in carcinogenesis

The CCN (Cyr61 (cysteine-rich protein 61), CTGF (connective tissue growth factor), Nov (nephroblastoma overexpressed)) family consists of six members that belong to matricellular proteins of extracellular matrix (ECM). Like other matricellular proteins, CCN members do not primarily have a structural role; however, they modulate cell-ECM interactions. In general, CCN proteins are formed by four characteristic domain structures and thought to participate in various biological phenomena such as organ development, wound healing, angiogenesis, fibrosis, etc. In cancer, CCN proteins family expresses aberrantly; probably depending on the sites and types, expressions of different CCN proteins have been documented to be linked with either progression or inhibition of the pathological processes of cancer. Through various mechanisms like cell survival, apoptosis, inflammation, cell adhesion and migration and connection with several cytokines, CCN proteins perhaps influence the disease course including tumor metastasis. A majority of the above-mentioned effects are believed to be mediated by binding with integrins, a class of receptors that mediate cell-cell and cell-ECM interactions. Furthermore, the members of CCN family modulate the functions of several important growth factors and related pathways such as insulin-like growth factor (IGF), transforming growth factor-beta (TGF-beta) and Wnt signaling. Interestingly, a variety of factors/proteins linked with these signaling systems are reported to be associated with the carcinogenic process. Nevertheless, a precise knowledge about the pathophysiological activities including signaling pathways of CCN proteins would be helpful to identify molecular targets in order to design therapeutic strategies in the management of cancer.