The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CYR61  -  cysteine-rich, angiogenic inducer, 61

Homo sapiens

Synonyms: CCN family member 1, CCN1, Cysteine-rich angiogenic inducer 61, GIG1, IBP-10, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CYR61


High impact information on CYR61

  • Members of the CCN (for CTGF, cyr61/cef10, nov) gene family encode cysteine-rich secreted proteins with roles in cell growth and differentiation [6].
  • Contrary to this paradigm, we show that fibroblast adhesion to the angiogenic matrix protein CCN1 (CYR61) induces apoptosis, whereas endothelial cell adhesion to CCN1 promotes cell survival [7].
  • Subsequent tests confirmed the presence of internal ribosome entry sites in the 5' noncoding regions of both Cyr61 and Pim-1 mRNAs [8].
  • In addition, the mRNA encoding Cyr61, a secreted factor that can promote angiogenesis and tumor growth, was selectively mobilized into polysomes when eIF4F concentrations were reduced, although its overall abundance changed only slightly [8].
  • Acting as an extracellular, matrix-associated signaling molecule, CYR61 promotes the adhesion of endothelial cells through interaction with the integrin alphaVbeta3 and augments growth factor-induced DNA synthesis in the same cell type [5].

Chemical compound and disease context of CYR61


Biological context of CYR61

  • First identified as the product of a growth factor-inducible immediate-early gene, CYR61 is an extracellular matrix-associated angiogenic inducer that functions as a ligand of integrin receptors to promote cell adhesion, migration, and proliferation [13].
  • This unique phenotype is correlated with impaired Vegf-C expression in the allantoic mesoderm, suggesting that CYR61-regulated expression of Vegf-C plays a role in vessel bifurcation [13].
  • To identify mAChR-inducible genes, we used a differential display approach and found that mAChRs rapidly induced transcription of the immediate early gene CYR61 in HEK 293 cells with a maximum expression after 1 h of receptor stimulation [14].
  • These findings help to define the mechanisms by which CYR61 acts as an angiogenic regulator, provide a molecular interpretation for the loss of vascular integrity and increased apoptosis of vascular cells in Cyr61-null mice, and underscore the importance of CYR61 in the development and homeostasis of the vascular system [15].
  • Here we show that CYR61 can also promote cell survival and tubule formation in human umbilical vein endothelial cells [15].

Anatomical context of CYR61

  • CYR61 deficiency results in a specific defect in vessel bifurcation (nonsprouting angiogenesis) at the chorioallantoic junction, leading to an undervascularization of the placenta without affecting differentiation of the labyrinthine syncytiotrophoblasts [13].
  • Stimulation of mAChRs induced CYR61 expression in primary neurons and rat brain where CYR61 mRNA was detected in cortical layers V and VI and in thalamic nuclei [14].
  • While fibroblasts and endothelial cells generally expressed good levels of all three CCN proteins, highly invasive MDA MB 231 cells expressed lower levels of CTGF and Nov, but higher levels of Cyr61, than the less invasive MCF-7 [16].
  • In this study, we show that purified CYR61 stimulates directed migration of human microvascular endothelial cells in culture through an alphaV beta3-dependent pathway and induces neovascularization in rat corneas [5].
  • Although CYR61 mRNA was synthesized in hyperplastic epithelial cells, in many cases of BPH, CYR61 protein was detected in both the epithelial and stromal regions of BPH patient tissues [10].

Associations of CYR61 with chemical compounds

  • Muscarinic acetylcholine receptors induce the expression of the immediate early growth regulatory gene CYR61 [14].
  • Increased CYR61 expression was coupled to mAChRs by both protein kinase C and elevations of intracellular Ca(2+) [14].
  • CYR61 is composed of four discrete structural domains that bear sequence similarities to the insulin-like growth factor-binding proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a carboxyl-terminal (CT) domain that resembles cysteine knots found in some growth factors [17].
  • It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloproteinases 1 and 3 [17].
  • We show that CYR61 encodes a 381 amino acid protein rich in cysteine and proline residues that is strongly conserved with the mouse homologue [18].
  • The CCN1-specific integrins alpha(M)beta(2) and alpha(V)beta(3) are expressed on CD34+ cells and CCN1 stimulated integrin-dependent signaling [19].

Regulatory relationships of CYR61


Other interactions of CYR61


Analytical, diagnostic and therapeutic context of CYR61


  1. Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features. Xie, D., Nakachi, K., Wang, H., Elashoff, R., Koeffler, H.P. Cancer Res. (2001) [Pubmed]
  2. Levels of expression of CYR61 and CTGF are prognostic for tumor progression and survival of individuals with gliomas. Xie, D., Yin, D., Wang, H.J., Liu, G.T., Elashoff, R., Black, K., Koeffler, H.P. Clin. Cancer Res. (2004) [Pubmed]
  3. Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associated with pre-eclampsia. Gellhaus, A., Schmidt, M., Dunk, C., Lye, S.J., Kimmig, R., Winterhager, E. Mol. Hum. Reprod. (2006) [Pubmed]
  4. Regulation of angiogenesis and endothelial cell function by connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61). Brigstock, D.R. Angiogenesis (2002) [Pubmed]
  5. CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth. Babic, A.M., Kireeva, M.L., Kolesnikova, T.V., Lau, L.F. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  6. Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. Hurvitz, J.R., Suwairi, W.M., Van Hul, W., El-Shanti, H., Superti-Furga, A., Roudier, J., Holderbaum, D., Pauli, R.M., Herd, J.K., Van Hul, E.V., Rezai-Delui, H., Legius, E., Le Merrer, M., Al-Alami, J., Bahabri, S.A., Warman, M.L. Nat. Genet. (1999) [Pubmed]
  7. The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts. Todorovicç, V., Chen, C.C., Hay, N., Lau, L.F. J. Cell Biol. (2005) [Pubmed]
  8. Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Johannes, G., Carter, M.S., Eisen, M.B., Brown, P.O., Sarnow, P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. The angiogenic factor CYR61 in breast cancer: molecular pathology and therapeutic perspectives. Menéndez, J.A., Mehmi, I., Griggs, D.W., Lupu, R. Endocr. Relat. Cancer (2003) [Pubmed]
  10. Increased expression of CYR61, an extracellular matrix signaling protein, in human benign prostatic hyperplasia and its regulation by lysophosphatidic acid. Sakamoto, S., Yokoyama, M., Zhang, X., Prakash, K., Nagao, K., Hatanaka, T., Getzenberg, R.H., Kakehi, Y. Endocrinology (2004) [Pubmed]
  11. The angiogenic factor Cyr61 is induced by the progestin R5020 and is necessary for mammary adenocarcinoma cell growth. Sampath, D., Winneker, R.C., Zhang, Z. Endocrine (2002) [Pubmed]
  12. Premenstrual regulation of the pro-angiogenic factor CYR61 in human endometrium. Gashaw, I., Stiller, S., Böing, C., Kimmig, R., Winterhager, E. Endocrinology (2008) [Pubmed]
  13. CYR61 (CCN1) is essential for placental development and vascular integrity. Mo, F.E., Muntean, A.G., Chen, C.C., Stolz, D.B., Watkins, S.C., Lau, L.F. Mol. Cell. Biol. (2002) [Pubmed]
  14. Muscarinic acetylcholine receptors induce the expression of the immediate early growth regulatory gene CYR61. Albrecht, C., von Der Kammer, H., Mayhaus, M., Klaudiny, J., Schweizer, M., Nitsch, R.M. J. Biol. Chem. (2000) [Pubmed]
  15. Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphavbeta3 and alpha6beta1 in human umbilical vein endothelial cells. Leu, S.J., Lam, S.C., Lau, L.F. J. Biol. Chem. (2002) [Pubmed]
  16. Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer. Jiang, W.G., Watkins, G., Fodstad, O., Douglas-Jones, A., Mokbel, K., Mansel, R.E. Endocr. Relat. Cancer (2004) [Pubmed]
  17. CYR61 stimulates human skin fibroblast migration through Integrin alpha vbeta 5 and enhances mitogenesis through integrin alpha vbeta 3, independent of its carboxyl-terminal domain. Grzeszkiewicz, T.M., Kirschling, D.J., Chen, N., Lau, L.F. J. Biol. Chem. (2001) [Pubmed]
  18. The human growth factor-inducible immediate early gene, CYR61, maps to chromosome 1p. Jay, P., Bergé-Lefranc, J.L., Marsollier, C., Méjean, C., Taviaux, S., Berta, P. Oncogene (1997) [Pubmed]
  19. The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration. Grote, K., Salguero, G., Ballmaier, M., Dangers, M., Drexler, H., Schieffer, B. Blood (2007) [Pubmed]
  20. A novel CYR61-triggered 'CYR61-alphavbeta3 integrin loop' regulates breast cancer cell survival and chemosensitivity through activation of ERK1/ERK2 MAPK signaling pathway. Menendez, J.A., Vellon, L., Mehmi, I., Teng, P.K., Griggs, D.W., Lupu, R. Oncogene (2005) [Pubmed]
  21. Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation. Lin, M.T., Chang, C.C., Chen, S.T., Chang, H.L., Su, J.L., Chau, Y.P., Kuo, M.L. J. Biol. Chem. (2004) [Pubmed]
  22. A critical role of Cyr61 in interleukin-17-dependent proliferation of fibroblast-like synoviocytes in rheumatoid arthritis. Zhang, Q., Wu, J., Cao, Q., Xiao, L., Wang, L., He, D., Ouyang, G., Lin, J., Shen, B., Shi, Y., Zhang, Y., Li, D., Li, N. Arthritis Rheum. (2009) [Pubmed]
  23. Induction and function of CYR61 (CCN1) in prostatic stromal and epithelial cells: CYR61 is required for prostatic cell proliferation. Sakamoto, S., Yokoyama, M., Aoki, M., Suzuki, K., Kakehi, Y., Saito, Y. Prostate (2004) [Pubmed]
  24. Elevated cysteine-rich 61 mediates aberrant collagen homeostasis in chronologically aged and photoaged human skin. Quan, T., He, T., Shao, Y., Lin, L., Kang, S., Voorhees, J.J., Fisher, G.J. Am. J. Pathol. (2006) [Pubmed]
  25. Vascular endothelial growth factor (VEGF)-induced up-regulation of CCN1 in osteoblasts mediates proangiogenic activities in endothelial cells and promotes fracture healing. Athanasopoulos, A.N., Schneider, D., Keiper, T., Alt, V., Pendurthi, U.R., Liegibel, U.M., Sommer, U., Nawroth, P.P., Kasperk, C., Chavakis, T. J. Biol. Chem. (2007) [Pubmed]
  26. Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria. Gashaw, I., Hastings, J.M., Jackson, K.S., Winterhager, E., Fazleabas, A.T. Biol. Reprod. (2006) [Pubmed]
  27. Comparison of prostaglandin F2alpha, bimatoprost (prostamide), and butaprost (EP2 agonist) on Cyr61 and connective tissue growth factor gene expression. Liang, Y., Li, C., Guzman, V.M., Evinger, A.J., Protzman, C.E., Krauss, A.H., Woodward, D.F. J. Biol. Chem. (2003) [Pubmed]
WikiGenes - Universities