CCN1/CYR61: the very model of a modern matricellular protein

Abstract

CCN1 (CYR61) is a dynamically expressed, multifunctional matricellular protein that plays essential roles in cardiovascular development during embryogenesis, and regulates inflammation, wound healing and fibrogenesis in the adult. Aberrant CCN1 expression is associated with myriad pathologies, including various cancers and diseases associated with chronic inflammation. CCN1 promotes diverse and sometimes opposing cellular responses, which can be ascribed, as least in part, to disparate activities mediated through its direct binding to distinct integrins in different cell types and contexts. Accordingly, CCN1 promotes cell proliferation, survival and angiogenesis by binding to integrins αvβ3, and induces apoptosis and senescence through integrin α6β1 and heparan sulfate proteoglycans. The ability of CCN1 to trigger the accumulation of a robust and sustained level of reactive oxygen species underlies some of its unique activities as a matrix cell-adhesion molecule. Emerging studies suggest that CCN1 might be useful as a biomarker or therapeutic target in certain diseases.

Knockdown of cysteine-rich 61 inhibits proliferation, migration, and invasiveness of prostate carcinoma PC-3 cells

“…It has become clear that diverse activities of Cyr61 can primarily be attributed to direct interaction to its distinct integrin receptors including a v b 3 , a 6 b 1 , a v b 5 , a 2 b 1 , a IIb b 3 , a M b 2 , and a D b 2 (Lau 2011). Binding of Cyr61 to integrins activates signaling enzymes such as phosphoinositide 3 (PI3)-kinase/Akt, ERK1/2, and MAPK, which are essential for cellular responses including cell proliferation, motility, survival, and invasiveness (Chong et al 2012).…”

Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output

“…They constitute molecular bridges between thymocytes and stromal cells, supporting migration and development of thymocytes and TEC [10][11][12][13] . CYR61 (CYsteine-Rich protein 61) is an ECM cell adhesive protein produced by several cells, including endothelial cells, fibroblasts and smooth muscle cells 14 . CYR61 has been implicated in carcinogenesis, wound healing and cardiovascular development through binding to integrins such as aVb3, aMb2 and a6b1 (refs [14][15][16][17].…”

“…CYR61 (CYsteine-Rich protein 61) is an ECM cell adhesive protein produced by several cells, including endothelial cells, fibroblasts and smooth muscle cells 14 . CYR61 has been implicated in carcinogenesis, wound healing and cardiovascular development through binding to integrins such as aVb3, aMb2 and a6b1 (refs [14][15][16][17]. Notably, Cyr61-deficient mice are embryonic lethal because of cardiovascular defects 18 .…”

“…Notably, Cyr61-deficient mice are embryonic lethal because of cardiovascular defects 18 . Depending on the cell type and context, CYR61 can promote the proliferation, survival, migration or senescence of cells 14,[17][18][19][20] . CYR61 is overexpressed in various cancer cells, including cancers of epithelial origin, and can promote their proliferation [21][22][23] .…”

“…As CYR61 promotes cell proliferation 14,16,21 , we examine here the benefits of CYR61 treatment on T-cell development and the thymic stroma. We observe that matricellular protein CYR61 specifically induces the proliferation of TEC and the expansion thymic stroma in vitro.…”