A structural approach to the role of CCN (CYR61/CTGF/NOV) proteins in tumourigenesis

Planque, Nathalie; Perbal, Bernard

doi:10.1186/1475-2867-3-15

Cited by 147 publications

(46 citation statements)

References 77 publications

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“…In CTGF, the C-terminal cystine knot domain is sufficient to mediate cell adhesion in a divalent cation-and heparin-dependent manner (70). Module IV is thought to act synergistically with module II in the formation of high molecular weight species (44,47).…”

Section: Discussionmentioning

confidence: 99%

“…CTGF belongs to the evolutionarily conserved CCN family of genes, which includes Cyr61 (cysteine-rich 61, also known as CCN1), CTGF (also known as CCN2), Nov (nephroblastoma overexpressed gene, also known as CCN3), WISP-1 (Wnt-1-induced secreted protein 1, also known as CCN4), WISP-2 (also known as CCN5), and WISP-3 (also known as CCN6) (43)(44)(45)(46)(47)(48). Human CTGF was identified as a mitogen present in the conditioned medium of human umbilical vein endothelial cells (66).…”

Section: Discussionmentioning

confidence: 99%

“…CTGF was also cloned from human chondrocytes as a hypertrophic chondrocyte-specific gene product 24 (or Hcs24) (68). The CCN proteins exhibit a common multimodular organization with structural motifs resembling insulin-like growth factor-binding proteins, von Willebrand factor, thrombospondin (TSP1), and the C-terminal cystine knot (43)(44)(45)(46)(47)(48). Among them, module IV is the least conserved of the four domains at the nucleotide level, but it appears to be critical for several of the biological functions attributed to the CCN proteins.…”

Section: Discussionmentioning

confidence: 99%

“…CTGF Promotes the Motility of Mesenchymal Stem CellsAlthough the biological functions of CTGF and other CCN family members are currently unknown, several lines of studies suggest that the CCN proteins may regulate multiple cellular processes, such as cell proliferation, migration, differentiation, angiogenesis, and skeletal development (43)(44)(45)(46)(47)(48)). Here we conducted three different but complementary experiments to investigate whether CTGF exerted any effect on the migratory features of mesenchymal stem cells.…”

Section: Constitutive Ctgf Expression Inhibits the Bmp-9-and Wnt3a-inmentioning

confidence: 99%

“…CTGF (also known as Fisp12, Hcs24, ecogenin, ␤IG-M2, IG-FBP8, and CCN2) is a member of the CCN (acronym for Cyr61, CTGF, and Nov) family that also includes Cyr61/CCN1, Nov/ CCN3, WISP1/CCN4, WISP2/CCN5, and WISP3/CCN6 (43)(44)(45)(46)(47)(48). The CCN proteins are secreted cysteine-rich multimodular proteins (43)(44)(45)(46)(47)(48). In this study, we sought to determine the functional role of CTGF in osteoblast differentiation induced by BMP-9 or Wnt3A.…”

mentioning

confidence: 99%

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Connective Tissue Growth Factor (CTGF) Is Regulated by Wnt and Bone Morphogenetic Proteins Signaling in Osteoblast Differentiation of Mesenchymal Stem Cells

Luo

Kang

et al. 2004

Journal of Biological Chemistry

292

356

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Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well regulated but poorly understood process. Both bone morphogenetic proteins (BMPs) and Wnt signaling are implicated in regulating osteoblast differentiation and bone formation. Here we analyzed the expression profiles of mesenchymal stem cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling. We confirmed the microarray results, and we demonstrated that CTGF was up-regulated at the early stage of BMP-9 and Wnt3A stimulations and that Wnt3A-regulated CTGF expression was ␤-catenin-dependent. RNA interference-mediated knockdown of CTGF expression significantly diminished BMP-9-induced, but not Wnt3A-induced, osteogenic differentiation, suggesting that Wnt3A may also regulate osteoblast differentiation in a CTGF-independent fashion. However, constitutive expression of CTGF was shown to inhibit both BMP-9-and Wnt3A-induced osteogenic differentiation. Exogenous expression of CTGF was shown to promote cell migration and recruitment of mesenchymal stem cells. Our findings demonstrate that CTGF is up-regulated by Wnt3A and BMP-9 at the early stage of osteogenic differentiation, which may regulate the proliferation and recruitment of osteoprogenitor cells; however, CTGF is down-regulated as the differentiation potential of committed pre-osteoblasts increases, strongly suggesting that tight regulation of CTGF expression may be essential for normal osteoblast differentiation of mesenchymal stem cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Constitutive Ctgf Expression Inhibits the Bmp-9-and Wnt3a-inmentioning

confidence: 99%

mentioning

confidence: 99%

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Connective Tissue Growth Factor (CTGF) Is Regulated by Wnt and Bone Morphogenetic Proteins Signaling in Osteoblast Differentiation of Mesenchymal Stem Cells

Luo

Kang

et al. 2004

Journal of Biological Chemistry

292

356

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Cyr61 downmodulation potentiates the anticancer effects of zoledronic acid in androgen‐independent prostate cancer cells

Marra

Santini

Meo

et al. 2009

Intl Journal of Cancer

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We have analyzed the gene modulation induced by zoledronic acid (ZOL) in androgen-resistant prostate cancer PC3 cells with cDNA microarray platform to identify new molecular targets of ZOL in prostate cancer. The gene coding for cysteine-rich, angiogenic inducer, 61 (CYR61) resulted highly downregulated with a fold change of 5.58. Therefore, we have studied the effects of ZOL on CYR61 protein product, and we have found that CYR61 protein expression was decreased significantly after exposure to ZOL. The effect of ZOL on CYR61 expression was dose and time dependent was due to a reduced transcriptional activity of CYR61 promoter. Moreover, the effects induced by ZOL were paralleled by decreased activation of Ras-Raf-1-and Akt-dependent pathways that was dependent from isoprenylation inhibition, since it was antagonized by the addition of geranylgeraniol. Finally, we have investigated the role of CYR61 in the regulation of growth inhibition and invasion/motility of PC3 cells using a shRNA for CYR61 to downregulate the expression of CYR61 protein. The enhanced inhibition of proliferation and motility/invasion induced by ZOL by S-phase accumulation. In the same experimental conditions, CYR61 protein downregulation potentiated the inactivation of the Ras-dependent proliferation pathway and cell cycle inhibitors p21 and p27 expression. ' 2009 UICC

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Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme

Ding

Chen

O’Kelly

et al. 2010

Intl Journal of Cancer

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Connective tissue growth factor (CTGF or CCN2) is a secreted protein that belongs to the CCN [cysteine-rich CYR61/CTGF/ nephroblastoma-overexpressed gene] family. These proteins have been implicated in various biological processes, including stimulation of cell proliferation, migration, angiogenesis and tumorigenesis. In a previous study, we found that CTGF mRNA was elevated in primary gliomas, and a significant correlation existed between CTGF mRNA levels versus tumor grade, histology and patient survival. In this study, the role of CTGF in glioma tumorigenesis was explored. Forced expression of CTGF in glioblastoma multiforme (GBM) cells accelerated their growth in liquid culture and soft agar, stimulated cells migration in Boyden chamber assays and significantly increased their ability to form large, vascularized tumors in nude mice. CTGF induced the expression of the antiapoptotic proteins, Bcl-xl, Survivin and Flip. Overexpression of CTGF caused the U343 GBM cells to survive for longer than 40 days in serum-free medium and resist antitumor drugs including tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand, VELCADE (bortezomib, proteasome inhibitor) and temozolomide. Our data suggest that CTGF plays an important role in glioma progression, by supporting tumor cells survival and drug resistance.

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A structural approach to the role of CCN (CYR61/CTGF/NOV) proteins in tumourigenesis

Cited by 147 publications

References 77 publications

Connective Tissue Growth Factor (CTGF) Is Regulated by Wnt and Bone Morphogenetic Proteins Signaling in Osteoblast Differentiation of Mesenchymal Stem Cells

Connective Tissue Growth Factor (CTGF) Is Regulated by Wnt and Bone Morphogenetic Proteins Signaling in Osteoblast Differentiation of Mesenchymal Stem Cells

Cyr61 downmodulation potentiates the anticancer effects of zoledronic acid in androgen‐independent prostate cancer cells

Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme

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