suppression of inflammatory arthritis. CYR61 is also found in articular cartilage from patients with osteoarthritis and appears to suppress ADAMTS4 (aggrecanase) activity, possibly leading to cartilage cell (chondrocyte) cloning. Vascular diseases CYR61 is overexpressed in vascular smooth muscle cells of atherosclerotic lesions and in the neointima of restenosis after balloon angioplasty, both in rodent models and in humans. Suppression of CYR61 expression results in reduced neointimal hyperplasia after balloon angioplasty, an effect that is reversed by delivery of CYR61 via gene transfer In a mouse model of oxygen-induced retinopathy, expression of CYR61 in the vitreous humor produced significant beneficial effects in repairing damaged vasculature. Cancer Angiogenesis is essential for the supply of oxygen and nutrients to nourish the growing tumor. CYR61 is a powerful angiogenic inducer in vivo, and it can also promote cancer cell proliferation, invasion, survival, epithelial–mesenchymal transition, and metastasis. Accordingly, forced overexpression of CYR61 enhanced tumor growth in xenografts of breast cancer cells, prostate cancer cells, ovarian carcinoma cells, and squamous carcinoma cells. Clinically, CYR61 expression correlates with the tumor stage, tumor size, lymph node positivity, and poor prognosis in several cancers, including breast cancer, prostate cancer, glioma, gastric adenocarcinoma, and squamous cell carcinoma. However, CYR61 can also induce apoptosis and cellular senescence, two well-established mechanisms of tumor suppression Thus, whereas CYR61 can promote the proliferation of prostate cancer cells, it can also exacerbate apoptosis of these cells in the presence of the immune surveillance molecule TRAIL. CYR61 has an inhibitory effect on some cancers, and suppresses tumor growth of non-small-cell lung cancer (NSCLC) cells, endometrial adenocarcinoma cells, and in melanoma cells. References Aging-related genes Aging-related proteins CCN proteins