The CCN family proteins in carcinogenesis

Experimental Oncology

Volumn 32, Issue 1, 2010, Pages 2-9

  Dhar, A ^a,b   Ray, A ^a  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

Author keywords

Angiogenesis; CCN family; Growth factor; Tumor; Wnt related protein

Indexed keywords

BONE MORPHOGENETIC PROTEIN; CONNECTIVE TISSUE GROWTH FACTOR; CYSTEINE RICH PROTEIN 61; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; INTEGRIN; MATRILYSIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NEPHROBLASTOMA OVEREXPRESSED PROTEIN; PROTEIN BCL XL; PROTEIN CCN; PROTEIN CCN4; PROTEIN CCN5; PROTEIN CCN6; PROTEIN KINASE B; PROTEIN P53; SCLEROPROTEIN; SOMATOMEDIN; SOMATOMEDIN BINDING PROTEIN; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERY LATE ACTIVATION ANTIGEN 2; VERY LATE ACTIVATION ANTIGEN 5; VERY LATE ACTIVATION ANTIGEN 6; VON WILLEBRAND FACTOR; WNT PROTEIN;

ANGIOGENESIS; APOPTOSIS; CANCER GROWTH; CARCINOGENESIS; CELL ADHESION; CELL INTERACTION; CELL MIGRATION; CELL SURVIVAL; DISEASE COURSE; FIBROSIS; HUMAN; INFLAMMATION; METASTASIS; NONHUMAN; ORGANOGENESIS; PATHOPHYSIOLOGY; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; WOUND HEALING;

ANIMALS; CCN INTERCELLULAR SIGNALING PROTEINS; CELL TRANSFORMATION, NEOPLASTIC; HUMANS; INFLAMMATION; MODELS, BIOLOGICAL; NEOPLASMS; SOMATOMEDINS; TRANSFORMING GROWTH FACTORS;

EID: 77950577197     PISSN: 18129269     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (89)

1. Holbourn KP, Acharya KR, Perbal B. The CCN family of proteins: Structure - function relationships. Trends Biochem Sci 2008; 33: 461-473.
2. Chen CC, Lau LF. Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol 2009; 41:771-783.
3. Kubota S, Takigawa M. CCN family proteins and angio-genesis: From embryo to adulthood. Angiogenesis 2007; 10:1-11.
4. Brigstock DR. Regulation of angiogenesis and endothe-lial cell function by connective tissue growth factor (CTGF) andcysteine-rich61 (CYR61). Angiogenesis 2002; 5:153-165.
5. Pan LH, Beppu T, Kurose A, et al. Neoplastic cells and proliferating endothelial cells express connective tissue growth factor(CTGF) inglioblastoma. Neurol Res 2002; 24:677-683.
6. Katsube K, Sakamoto K, Tamamura Y, et al. Role of CCN, a vertebrate specific gene family, in development. Dev Growth Differ 2009; 51: 55-67.
7. Rho SB, Woo JS, Chun T, et al. Cysteine-rich 61 (CYR61) inhibits cisplatin-induced apoptosis in ovarian carcinoma cells. Biotechnol Lett 2009; 31: 23-28.
8. Fujisawa T, Hattori T, Ono M, et al. CCN family 2/connective tissue growth factor (CCN2/CTGF) stimulates proliferation and differentiation of auricular chondrocytes. Osteoarthritis Cartilage 2008; 16: 787-795.
9. Hishikawa K, Oemar BS, Tanner FC, et al. Connective tissue growth factor induces apoptosis in human breast cancer cell line MCF-7. J Biol Chem 1999; 274: 37461-37466.
10. Croci S, Landuzzi L, Astolfi A, et al. Inhibition of connective tissue growth factor (CTGF/CCN2) expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells. Cancer Res 2004; 64: 1730-1736.
11. Xie D, Nakachi K, Wang H, et al. Elevated levels of connective tissue growth factor, WISP-1 and CYR61 in primary breast cancers associated with more advanced features. Cancer Res 2001; 61: 8917-8923.
12. Jiang WG, Watkins G, Fodstad O, et al. Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer. Endocr Relat Cancer 2004; 11:781-791.
13. Sampath D, Winneker RC, Zhang Z. Cyr61, a member of the CCN family, is required for MCF-7 cell proliferation: Regulation by 17 beta-estradiol and overexpression in human breast cancer. Endocrinology 2001; 142: 2540-2548.
14. Tsai MS, Bogart DF, Castaneda JM, et al. Cyr61 promotes breast tumorigenesis and cancer progression. Oncogene 2002; 21: 8178-8185.
15. Lin MT, Chang CC, Chen ST, et al. Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation. J Biol Chem 2004; 279: 24015-24023.
16. Watari H, Xiong Y, Hassan MK, et al. Cyr61, a member of CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family predicts survival of patients with endometrial cancer of endometrioid subtype. Gynecol Oncol 2009; 112: 229-234.
17. Chien W, Kumagai T, Miller CW, et al. Cyr61 suppresses growth of human endometrial cancer cells. J Biol Chem 2004; 279: 53087-53096.
18. Gery S, Xie D, Yin D, et al. Ovarian carcinomas: CCN genes are aberrantly expressed and CCN 1 promotes proliferation of these cells. Clin Cancer Res 2005; 11: 7243-7254.
19. Maeta N, Osaki M, Shomori K, et al. CYR61 down-regulation correlates with tumor progression by promoting MMP-7 expression in human gastric carcinoma. Oncology 2007; 73: 118-126.
20. Lin MT, Kuo IH, Chang CC, et al. Involvement of hypoxia-inducing factor-1 alpha-dependent plasminogen activator inhibitor-1 up-regulation in Cyr61/CCN1-induced gastric cancer cell invasion. J Biol Chem 2008; 283:15807-15815.
21. Sin WC, Bechberger JF, Rushlow WJ, et al. Dose-dependent differential upregulation of CCN 1/Cyr61 and CCN3/Nov by the gap junction protein Connexin 43 in glioma cells. J Cell Biochem 2008; 103: 1772-1782.
22. Xie D, Yin D, Wang HJ, et al. Levels of expression of CYR61 and CTGF are prognostic for tumor progression and survival of individuals with gliomas. Clin Cancer Res 2004; 10: 2072-2081.
23. Chen PP, Li WJ, Wang Y, et al. Expression of Cyr61, CTGF, and WISP-1 correlates with clinical features of lung cancer. PLoS ONE 2007; 2: e534.
24. Tong X, Xie D, O'Kelly J, et al. Cyr61, a member of CCN family, is a tumor suppressor in non-small cell lung cancer. J Biol Chem 2001; 276: 47709-47714.
25. Chien W, Yin D, Gui D, et al. Suppression of cell proliferation and signaling transduction by connective tissue growth factor in non-small cell lung cancer cells. Mol Cancer Res 2006; 4:591-598.
26. Li MH, Sanchez T, Pappalardo A, et al. Induction of antiproliferative connective tissue growth factor expression in Wilms' tumor cells by sphingosine-1-phosphate receptor 2. Mol Cancer Res 2008; 6:1649-1656.
27. Kikuchi R, Tsuda H, Kanai Y, et al. Promoter hyper-methylation contributes to frequent inactivation of a putative conditional tumor suppressor gene connective tissue growth factor in ovarian cancer. Cancer Res 2007; 67: 7095-7105.
28. Gardini A, Corti B, Fiorentino M, et al. Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma. Dig Liver Dis 2005; 37: 269-274.
29. Deng YZ, Chen PP, Wang Y, et al. Connective tissue growth factor is overexpressed in esophageal squamous cell carcinoma and promotes tumorigenicity through beta-catenin-T-cell factor/Lef signaling. J Biol Chem 2007; 282:36571-36581.
30. Croci S, Landuzzi L, Nicoletti G, et al. Expression of connective tissue growth factor (CTGF/CCN2) in a mouse model of rhabdomyosarcomagenesis. Pathol Oncol Res 2007; 13:336-339.
31. Bleau AM, Planque N, Perbal B. CCN proteins and cancer: Two to tango. Front Biosci 2005; 10: 998-1009.
32. Manara MC, Perbal B, Benini S, et al. The expression of CCN3 (NOV) gene in musculoskeletal tumors. Am J Pathol 2002; 160: 849-859.
33. Benini S, Perbal B, Zambelli D, et al. In Ewing's sarcoma CCN3 (NOV) inhibits proliferation while promoting migration and invasion ofthe same cell type. Oncogene 2005; 24:4349-4361.
34. Vallacchi V, Daniotti M, Ratti F, et al. CCN3/nephro-blastoma overexpressed matricellular protein regulates integrin expression, adhesion, and dissemination in melanoma. Cancer Res 2008; 68: 715-723.
35. Bohlig L, Metzger R, Rother K, et al. The CCN3 gene coding for an extracellular adhesion-related protein is transcriptionally activated by the p53 tumor suppressor. Cell Cycle 2008; 7:1254-1261.
36. Yu C, Le AT, Yeger H, et al. NOV(CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia. J Pathol 2003; 201:609-615.
37. Khor TO, Gul YA, Ithnin H, et al. A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D 1 in colorectalcarcinoma. Int J Colorectal Dis 2006; 21:291-300.
38. Tian C, Zhou ZG, Meng WJ, et al. Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancerpatients. World J Gastroenterol 2007; 13:3878-3882.
39. Margalit O, Eisenbach L, Amariglio N, et al. Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines. Br J Cancer 2003; 89: 314-319.
40. Su F, Overholtzer M, Besser D, et al. WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. Genes Dev 2002; 16:46-57.
41. Soon LL, Yie TA, Shvarts A, et al. Overexpression of WISP-1 down-regulated motility and invasion of lung cancer cells through inhibition of Rac activation. J Biol Chem 2003; 278: 11465-11470.
42. Dhar G, Mehta S, Banerjee S, et al. Loss of WISP-2/CCN5 signaling in human pancreatic cancer: A potential mechanism for epithelial-mesenchymal- transition. Cancer Lett 2007; 254:63-70.
43. Kouzu Y, Uzawa K, Kato M, et al. WISP-2 expression in human salivary gland tumors. Int J Mol Med 2006; 17:567-573.
44. Inadera H, Hashimoto S, Dong HY, et al. WISP-2 as a novel estrogen-responsive gene in human breast cancer cells. Biochem Biophys Res Commun 2000; 275: 108-114.
45. Banerjee S, Saxena N, Sengupta K, et al. WISP-2 gene in human breast cancer: Estrogen and progesterone inducible expression and regulation of tumor cell proliferation. Neoplasia 2003; 5: 63-73.
46. Fritah A, Redeuilh G, Sabbah M. Molecular cloning and characterization of the human WISP-2/CCN5 gene promoter reveal its upregulation by oestrogens. J Endocrinol 2006; 191:613-624.
47. Ray G, Banerjee S, Saxena NK, et al. Stimulation of MCF-7 tumor progression in athymic nude mice by 17 beta-estradiol induces WISP-2/CCN5 expression in xenografts: Anovel signaling molecule in hormonal carcinogenesis. Oncol Rep 2005; 13:445-448.
48. Fritah A, Saucier C, De Wever O, et al. Role of WISP-2/CCN5 in the maintenance of a differentiated and non invasive phenotype in human breast cancer cells. Mol Cell Biol 2008; 28: 1114-1123.
49. Banerjee S, Dhar G, Haque I, et al. CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression ofthe disease and suppresses the invasive phenotypes of tumor cells. Cancer Res 2008; 68: 7606-7612.
50. Dhar G, Banerjee S, Dhar K, et al. Gain of oncogenic function of p53 mutants induces invasive phenotypes in human breast cancer cells by silencing CCN5/WISP-2. Cancer Res 2008; 68: 4580-4587.
51. Davies SR, Watkins G, Mansel RE, et al. Differential expression and prognostic implications of the CCN family members WISP-1, WISP-2, and WISP-3 in human breast cancer. Ann Surg Oncol 2007; 14: 1909-1918.
52. Kleer CG, Zhang Y, Merajver SD. CCN6 (WISP3) as a new regulator ofthe epithelial phenotype in breast cancer. Cells Tissues Organs 2007; 185: 95-99.
53. Lin EY, Pollard JW. Macrophage: Modulators of breast cancer progression. Novartis Found Symp 2004; 256:158-168.
54. Schafer M, Werner S. Cancer as an overhealing wound: An old hypothesis revisited. Nat Rev Mol Cell Biol 2008; 9: 628-638.
55. Sangaletti S, Colombo MP. Matricellular proteins at the crossroad of inflammation and cancer. Cancer Lett 2008; 267: 245-253.
56. Yoshida K, Munakata H. Connective tissue growth factor binds to fibronectin through the type I repeat modules and enhances the affinity of fibronectin to fibrin. Biochim Biophys Acta 2007; 1770: 672-680.
57. Shi-Wen X, Leask A, Abraham D. Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosis. Cytokine Growth Factor Rev 2008; 19:133-144.
58. Wiedmaier N, Muller S, Koberle M, et al. Bacteria induce CTGF and CYR61 expression in epithelial cells in a lysophosphatidic acid receptor-dependent manner. Int J Med Microbiol 2008; 298: 231-243.
59. Chen CC, Mo FE, Lau LF. The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts. J Biol Chem 2001; 276: 47329-47337.
60. Dalgleish AG, O'Byrne K. Inflammation and cancer: The role of the immune response and angiogenesis. Cancer Treat Res 2006; 130:1-38.
61. Pell JM, Salih DA, Cobb LJ, et al. The role insulin-like growth factor binding proteins in development. Rev Endocr Metab Disord 2005; 6: 189-198.
62. Flint DJ, Tonner E, Beattie J, et al. Role of insulin-like growth factor binding proteins in mammary gland development. J Mammary Gland Biol Neoplasia 2008; 13: 443-453.
63. Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev 1999; 20:761-787. (Pubitemid 30648894)
64. Smerdel-Ramoya A, Zanotti S, Stadmeyer L, et al. Skeletal overexpression of connective tissue growth factor impairs bone formation and causes osteopenia. Endocrinology 2008; 149: 4374-4381.
65. Dhar K, Banerjee S, Dhar G, et al. Insulin-like growth factor-1 (IGF-1) induces WISP-2/CCN5 via multiple molecular cross-talks and is essential for mitogenic switch by IGF-1 axis in estrogen receptor-positive breast tumor cells. Cancer Res 2007; 67: 1520-1526.
66. Kleer CG, Zhang Y, Pan Q, et al. WISP3 (CCN6) is a secreted tumor-suppressor protein that modulates IGF signaling in inflammatory breast cancer. Neoplasia 2004; 6:179-185.
67. Zhang Y, Pan Q, Zhong H, et al. Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells. Breast Cancer Res 2005; 7: R1080-R1089.
68. Glasgow E, Mishra L. Transforming growth factor-β signaling and ubiquitinators in cancer. Endocr Relat Cancer 2008; 15: 59-72.
69. Massague J. TGF beta in cancer. Cell 2008; 134:215-230.
70. Moritani NH, Kubota S, Sugahara T, et al. Comparable response of CCN1 with CCN2 genes upon arthritis: An in vitro evaluation with a human chondrocytic cell line stimulated by a set of cytokines. Cell Commun Signal 2005; 3: 6-13.
71. Parisi MS, Gazzerro E, Rvdziel S, et al. Expression and regulation of CCN genes in murine osteoblasts. Bone 2006; 38:671-677.
72. Luo X, Ding L, Chegini N. CCNs, fibulin-1C and S100A4 expression in leiomyoma and myometrium: Inverse association with TGF-beta and regulation by TGF-beta in leiomyoma and myometrial smooth muscle cells. Mol Hum Reprod 2006; 12: 245-256.
73. Leask A, Abraham DJ. The role of connective tissue growth factor, a multifunctional matricellular protein, in fi-broblast biology. Biochem Cell Biol 2003; 81: 355-363.
74. Mason RM. Connective tissue growth factor (CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it? J Cell Commun Signal 2009; 3: 95-104.
75. Askari JA, Buckley PA, Mould AP, et al. Linking inte-grin conformation to function. J Cell Sci 2009; 122: 165-170.
76. Avraamides CJ, Garmy-Susini B, Varner JA. Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 2008; 8:604-617.
77. Leu SJ, Lam SC, Lau LF. Pro-angiogenic activities of CYR61 (CCN 1) mediated through integrins alpha v beta 3 and alpha 6 beta 1 in human umbilical vein endothelial cells. J Biol Chem 2002; 277: 46248-46255.
78. Xie D, Yin D, Tong X, et al. Cyr61 is overexpressed in gliomas and involved in integrin-linked kinase-mediated Akt and beta-catenin-TCF/Lef signaling pathways. Cancer Res 2004; 64: 1987-1996.
79. Lin CG, Chen CC, Leu SJ, et al. Integrin-dependent functions of the angiogenic inducer NOV (CCN3): Implication in wound healing. J Biol Chem 2005; 280: 8229-8237.
80. Taneyhill L, Pennica D. Identification of Wnt responsive genes using a murine mammary epithelial cell line model system. BMC Dev Biol 2004; 4: 6-19.
81. Fuerer C, Nusse R, Berge D. Wnt signalling in development and disease. EMBO Rep 2008; 9: 134-138.
82. Latinkic BV, Mercurio S, Bennett B, et al. Xenopus Cyr61 regulates gastrulation movements and modulates Wnt signalling. Development 2003; 130: 2429-2441.
83. Si W, Kang Q, Luu HH, et al. CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells. Mol Cell Biol 2006; 26: 2955-2964.
84. Mercurio S, Latinkic B, Itasaki N, et al. Connective-tissue growth factor modules WNT signalling and interacts with the WNT receptor complex. Development 2004; 131:2137-2147.
85. Smerdel-Ramoya A, Zanotti S, Deregowski V, et al. Connective tissue growth factor enhances osteoblastogenesis in vitro. J Biol Chem 2008; 283: 22690-22699.
86. Canalis E. Nephroblastoma overexpressed (Nov) is a novel bone morphogenetic protein antagonist. Ann NY Acad Sci 2007; 1116: 50-58.
87. Rydziel S, Stadmeyer L, Zanotti S, et al. Nephroblastoma overexpressed (Nov) inhibits osteoblastogenesis and causes osteopenia. J Biol Chem 2007; 282: 19762-19772.
88. Xu L, Corcoran RB, Welsh JW, et al. WISP-1 is a Wnt-1- and β-catenin-responsive oncogene. Genes Dev 2000; 14: 585-595.
89. Nakamura Y, Weidinger G, Liang JO, et al. The CCN family member Wisp3, mutant in progressive pseudorheu-matoid dysplasia, modulates BMP and Wnt signaling. J Clin Invest 2007; 117: 3075-3086.