The influence of CCN family proteins on ovarian physiology and pathology

The CCN family of proteins is comprised of six matricellular proteins known to regulate multiple cellular processes such as adhesion, proliferation, differentiation, and apoptosis. CCN proteins are known to function through the binding of integrin receptors and through the regulation of growth factors and cytokines in the context of cardiovascular and skeletal development, injury repair, fibrosis, inflammation and cancer. The expression and roles of several CCNs, particularly CCN1 and CCN2, have been investigated in the ovary as they are effectors of the Hippo signaling pathway, and their role in the development of ovarian fibrosis has been described. Here we review the patterns of expression of CCN1-6 in the ovarian follicle, and the role of CCN2 in follicle development and steroidogenesis, and the expression and potential actions of CCN1-6 in ovarian cancers. We highlight the roles CCNs may play in inflammatory processes, and put forth a case for CCN involvement in the process of ovulation.