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Lester F Lau - One of the best experts on this subject based on the ideXlab platform.

  • taking aim at the extracellular matrix CCN Proteins as emerging therapeutic targets
    Nature Reviews Drug Discovery, 2011
    Co-Authors: Joon Il Jun, Lester F Lau
    Abstract:

    Members of the CCN family of matricellular Proteins are crucial for embryonic development and have important roles in inflammation, wound healing and injury repair in adulthood. Deregulation of CCN Protein expression or activities contributes to the pathobiology of various diseases — many of which may arise when inflammation or tissue injury becomes chronic — including fibrosis, atherosclerosis, arthritis and cancer, as well as diabetic nephropathy and retinopathy. Emerging studies indicate that targeting CCN Protein expression or signalling pathways holds promise in the development of diagnostics and therapeutics for such diseases. This Review summarizes the biology of CCN Proteins, their roles in various pathologies and their potential as therapeutic targets.

  • 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
    Journal of Biological Chemistry, 2001
    Co-Authors: Tatiana M Grzeszkiewicz, Ningyu Chen, Deborah J Kirschling, Lester F Lau
    Abstract:

    Abstract CYR61, an angiogenic factor and a member of the CCN Protein family, is an extracellular matrix-associated, heparin-binding Protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloProteinases 1 and 3. 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. In this study, we show that a CYR61 mutant (CYR61ΔCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin αvβ5 but not integrins α6β1 or αvβ3. Furthermore, we show that CYR61 binds directly to purified integrin αvβ5 in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin αvβ3, a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins α6β1, αvβ5, and αvβ3, respectively. Together, these findings establish CYR61 as a novel ligand for integrin αvβ5 and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.

  • cyr61 stimulates human skin fibroblast migration through integrin αvβ5 and enhances mitogenesis through integrin αvβ3 independent of its carboxyl terminal domain
    Journal of Biological Chemistry, 2001
    Co-Authors: Tatiana M Grzeszkiewicz, Ningyu Chen, Deborah J Kirschling, Lester F Lau
    Abstract:

    CYR61, an angiogenic factor and a member of the CCN Protein family, is an extracellular matrix-associated, heparin-binding Protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloProteinases 1 and 3. 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. In this study, we show that a CYR61 mutant (CYR61ΔCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin αvβ5 but not integrins α6β1 or αvβ3. Furthermore, we show that CYR61 binds directly to purified integrin αvβ5 in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin αvβ3, a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins α6β1, αvβ5, and αvβ3, respectively. Together, these findings establish CYR61 as a novel ligand for integrin αvβ5 and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.

Ningyu Chen - One of the best experts on this subject based on the ideXlab platform.

  • CCN3 nov is a novel angiogenic regulator of the CCN Protein family
    Journal of Biological Chemistry, 2003
    Co-Authors: Ningyu Chen, Christopher M Tebeau, Choyau Yeung
    Abstract:

    Abstract CCN3 (NOV) is a matricellular Protein of the CCN family, which also includes CCN1 (CYR61), CCN2 (CTGF), CCN4 (WISP-1), CCN5 (WISP-2), and CCN6 (WISP-3). During development, CCN3 is expressed widely in derivatives of all three germ layers, and high levels of expression are observed in smooth muscle cells of the arterial vessel wall. Altered expression of CCN3 has been observed in a variety of tumors, including hepatocellular carcinomas, Wilm's tumors, Ewing's sarcomas, gliomas, rhabdomyosarcomas, and adrenocortical carcinomas. To understand its biological functions, we have investigated the activities of purified recombinant CCN3. We show that in endothelial cells, CCN3 supports cell adhesion, induces directed cell migration (chemotaxis), and promotes cell survival. Mechanistically, CCN3 supports human umbilical vein endothelial cell adhesion through multiple cell surface receptors, including integrins αvβ3, α5β1, α6β1, and heparan sulfate proteoglycans. In contrast, CCN3-induced cell migration is dependent on integrins αvβ3 and α5β1, whereas α6β1 does not play a role in this process. Although CCN3 does not contain a RGD sequence, it binds directly to immobilized integrins αvβ3 and α5β1, with half-maximal binding occurring at 10 nm and 50 nm CCN3, respectively. Furthermore, CCN3 induces neovascularization when implanted in rat cornea, demonstrating that it is a novel angiogenic inducer. Together, these findings show that CCN3 is a ligand of integrins αvβ3 and α5β1, acts directly upon endothelial cells to stimulate pro-angiogenic activities, and induces angiogenesis in vivo.

  • 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
    Journal of Biological Chemistry, 2001
    Co-Authors: Tatiana M Grzeszkiewicz, Ningyu Chen, Deborah J Kirschling, Lester F Lau
    Abstract:

    Abstract CYR61, an angiogenic factor and a member of the CCN Protein family, is an extracellular matrix-associated, heparin-binding Protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloProteinases 1 and 3. 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. In this study, we show that a CYR61 mutant (CYR61ΔCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin αvβ5 but not integrins α6β1 or αvβ3. Furthermore, we show that CYR61 binds directly to purified integrin αvβ5 in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin αvβ3, a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins α6β1, αvβ5, and αvβ3, respectively. Together, these findings establish CYR61 as a novel ligand for integrin αvβ5 and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.

  • cyr61 stimulates human skin fibroblast migration through integrin αvβ5 and enhances mitogenesis through integrin αvβ3 independent of its carboxyl terminal domain
    Journal of Biological Chemistry, 2001
    Co-Authors: Tatiana M Grzeszkiewicz, Ningyu Chen, Deborah J Kirschling, Lester F Lau
    Abstract:

    CYR61, an angiogenic factor and a member of the CCN Protein family, is an extracellular matrix-associated, heparin-binding Protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloProteinases 1 and 3. 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. In this study, we show that a CYR61 mutant (CYR61ΔCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin αvβ5 but not integrins α6β1 or αvβ3. Furthermore, we show that CYR61 binds directly to purified integrin αvβ5 in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin αvβ3, a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins α6β1, αvβ5, and αvβ3, respectively. Together, these findings establish CYR61 as a novel ligand for integrin αvβ5 and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.

Tatiana M Grzeszkiewicz - One of the best experts on this subject based on the ideXlab platform.

  • 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
    Journal of Biological Chemistry, 2001
    Co-Authors: Tatiana M Grzeszkiewicz, Ningyu Chen, Deborah J Kirschling, Lester F Lau
    Abstract:

    Abstract CYR61, an angiogenic factor and a member of the CCN Protein family, is an extracellular matrix-associated, heparin-binding Protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloProteinases 1 and 3. 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. In this study, we show that a CYR61 mutant (CYR61ΔCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin αvβ5 but not integrins α6β1 or αvβ3. Furthermore, we show that CYR61 binds directly to purified integrin αvβ5 in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin αvβ3, a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins α6β1, αvβ5, and αvβ3, respectively. Together, these findings establish CYR61 as a novel ligand for integrin αvβ5 and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.

  • cyr61 stimulates human skin fibroblast migration through integrin αvβ5 and enhances mitogenesis through integrin αvβ3 independent of its carboxyl terminal domain
    Journal of Biological Chemistry, 2001
    Co-Authors: Tatiana M Grzeszkiewicz, Ningyu Chen, Deborah J Kirschling, Lester F Lau
    Abstract:

    CYR61, an angiogenic factor and a member of the CCN Protein family, is an extracellular matrix-associated, heparin-binding Protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloProteinases 1 and 3. 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. In this study, we show that a CYR61 mutant (CYR61ΔCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin αvβ5 but not integrins α6β1 or αvβ3. Furthermore, we show that CYR61 binds directly to purified integrin αvβ5 in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin αvβ3, a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins α6β1, αvβ5, and αvβ3, respectively. Together, these findings establish CYR61 as a novel ligand for integrin αvβ5 and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.

Deborah J Kirschling - One of the best experts on this subject based on the ideXlab platform.

  • 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
    Journal of Biological Chemistry, 2001
    Co-Authors: Tatiana M Grzeszkiewicz, Ningyu Chen, Deborah J Kirschling, Lester F Lau
    Abstract:

    Abstract CYR61, an angiogenic factor and a member of the CCN Protein family, is an extracellular matrix-associated, heparin-binding Protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloProteinases 1 and 3. 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. In this study, we show that a CYR61 mutant (CYR61ΔCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin αvβ5 but not integrins α6β1 or αvβ3. Furthermore, we show that CYR61 binds directly to purified integrin αvβ5 in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin αvβ3, a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins α6β1, αvβ5, and αvβ3, respectively. Together, these findings establish CYR61 as a novel ligand for integrin αvβ5 and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.

  • cyr61 stimulates human skin fibroblast migration through integrin αvβ5 and enhances mitogenesis through integrin αvβ3 independent of its carboxyl terminal domain
    Journal of Biological Chemistry, 2001
    Co-Authors: Tatiana M Grzeszkiewicz, Ningyu Chen, Deborah J Kirschling, Lester F Lau
    Abstract:

    CYR61, an angiogenic factor and a member of the CCN Protein family, is an extracellular matrix-associated, heparin-binding Protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloProteinases 1 and 3. 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. In this study, we show that a CYR61 mutant (CYR61ΔCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin αvβ5 but not integrins α6β1 or αvβ3. Furthermore, we show that CYR61 binds directly to purified integrin αvβ5 in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin αvβ3, a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins α6β1, αvβ5, and αvβ3, respectively. Together, these findings establish CYR61 as a novel ligand for integrin αvβ5 and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.

Ruth Chiquetehrismann - One of the best experts on this subject based on the ideXlab platform.

  • CCN4 wisp1 wnt1 inducible signaling pathway Protein 1 a focus on its role in cancer
    The International Journal of Biochemistry & Cell Biology, 2015
    Co-Authors: Irem Gurbuz, Ruth Chiquetehrismann
    Abstract:

    The matricellular Protein WISP1 is a member of the CCN Protein family. It is induced by WNT1 and is a downstream target of β-catenin. WISP1 is expressed during embryonic development, wound healing and tissue repair. Aberrant WISP1 expression is associated with various pathologies including osteoarthritis, fibrosis and cancer. Its role in tumor progression and clinical outcome makes WISP1 an emerging candidate for the detection and treatment of tumors.