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  • Gorantla, Bharathi  (4)
  • 1
    Online-Ressource
    Online-Ressource
    Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Regulation of WNT/β-Catenin Signaling Is Enhanced in Irradiated Medulloblastoma Cells
    Elsevier BV ; 2012
    In:  Journal of Biological Chemistry Vol. 287, No. 24 ( 2012-06), p. 20576-20589
    Details
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 287, No. 24 ( 2012-06), p. 20576-20589
    Materialart: Online-Ressource
    ISSN: 0021-9258
    URL: Article
    DOI: 10.1074/jbc.M112.348888
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2012
    ZDB Id: 2141744-1
    ZDB Id: 1474604-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 2
    Online-Ressource
    Online-Ressource
    Abstract 4060: Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4060-4060
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4060-4060
    Kurzfassung: Stereospecific radiation treatment offers a distinct opportunity for temporal and spatial regulation of gene expression at tumor sites by means of inducible promoters. To achieve this, a plasmid, pCArG-U2, was constructed by incorporating nine CArG elements (in tandem) of EGR1 gene upstream to uPA and uPAR siRNA oligonucleotides in a pCi-Neo vector. Radiation-induced siRNA expression was detected in a meningioma cell line (IOMM-Lee). Immunoblotting and RT-PCR analyses confirmed downregulation of uPA and uPAR. A similar effect was observed in transfected cells followed by H2O2 treatment. Moreover, pre-treatment of transfected cells with N-Acetyl L-Cysteine blocked the silencing of uPA and uPAR, which further confirmed the oxidative damage-mediated downregulation. Cell proliferation assays and western blot analysis for apoptotic molecules confirmed cell death in a radiation-inducible fashion. Migration and Matrigel invasion assays also revealed a marked decrease in the migration and invasive behavior. Immunocytochemistry showed a marked decrease in uPA and uPAR levels in the transfected and irradiated cells. H & E staining revealed a decrease in the pre-established tumor volume among the animals treated with pCArG-U2 and radiation. Immunohistochemistry of the brain sections established with intracranial tumors also revealed a marked decrease in uPA and uPAR in a radiation-inducible fashion. Altogether, our data suggest pCArG-U2 as a suitable candidate for radiation-inducible gene therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4060.
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-4060
    RVK:
    XA 36000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2010
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    Abstract 3904: uPAR-regulated nuclear translocation of hand-1 mediates vascular radiosensitivity in medulloblastoma tumors.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 3904-3904
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 3904-3904
    Kurzfassung: Urokinase-type plasminogen activator (uPAR) is overexpressed in the tumor-stromal invasive microenvironment in many human cancers including medulloblastoma. The role of uPAR in tumor progression and angiogenesis has been well characterized. Most recently, in medulloblastoma cells, we showed that ionizing radiation (IR)-induced uPAR is a potent activator of cancer stem cell (CSC)-like properties and is associated with various transcription factors that are involved during embryonic development and cancer. In this study, we show that the uPAR protein is a cytoplasmic sequestration factor for a novel basic helix-loop-helix (bHLH) transcription factor, Hand-1. The Hand-1 protein plays an essential role in differentiation of trophoblast giant cells and cardiac morphogenesis, and yet its precise cellular function and its contributions to cancer remain mostly unknown. In the present study, we observed that Hand-1 protein is upregulated in uPAR shRNA-treated medulloblastoma cells and accompanies sustained cell growth and angiogenesis. Furthermore, IR-induced uPAR overexpression negatively regulates Hand-1 activity and results in the stabilization of angiogenesis promoting molecules, such as HIF-1 alpha. Finally, uPAR overexpression and its association with Hand-1 after IR treatment indicate that uPAR is capable of regulating Hand-1 and that uPAR has a role in the process of IR-induced tumor angiogenesis. Citation Format: Swapna Asuthkar, Kiran Kumar Velpula, Arun Kumar Nalla, Venkateswara Rao Gogineni, Venkata Ramesh Dasari, Bharathi Gorantla, Jasti S. Rao. uPAR-regulated nuclear translocation of hand-1 mediates vascular radiosensitivity in medulloblastoma tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3904. doi:10.1158/1538-7445.AM2013-3904
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-3904
    RVK:
    XA 36000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2013
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    Abstract 5212: Irradiation-induced uPAR promotes stemness via Wnt/β-catenin signaling in medulloblastoma cells
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5212-5212
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5212-5212
    Kurzfassung: Urokinase plasminogen activator receptor (uPAR) is known to promote invasion, migration and metastasis in cancer cells. In this study, we show that ionizing radiation (IR) induced uPAR has a role in Wnt/β-catenin signaling and mediates induction of cancer stem cells (CSC)-like properties in medulloblastoma cell lines UW228 and D283. We observed that IR induced the expression of uPAR, CSC markers such as CD44 and Msi-1, and activates Wnt/β-catenin signaling molecules. Overexpression of uPAR after IR treatment led to the activation of Wnt signaling, which was demonstrated by an increase in nuclear translocation of β-catenin and β-catenin-Lef/Tcf-mediated transactivation, thereby promoting cancer stemness. Quercetin, a potent Wnt/β-catenin inhibitor suppressed uPAR and uPAR-mediated Wnt/β-catenin activation. Treatment with shRNA specific for uPAR (pU) suppressed the β-catenin-Tcf/Lef-mediated transactivation both in vitro and in vivo. Further, we show that uPAR is physically associated with the Wnt effector molecule β-catenin using immunocytochemistry and immunohistochemistry; these results were confirmed by immunoprecipitation analysis. Most interestingly, we demonstrate for the first time that the localization of uPAR in the nucleus is associated with transcription factors (TF) and their specific response elements. The association of uPAR with β-catenin-Tcf/Lef complex and various other TF involved in neurogenesis during embryonic development and cancer demonstrates the receptor's possible role at generating CSC-like properties in primitive neuroectodermal tumor (PNET) cells of medulloblastoma. Considering all of the data, we conclude that uPAR is a potent activator of stemness, and the targeting of uPAR in combination with radiation has significant therapeutic implications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5212. doi:1538-7445.AM2012-5212
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-5212
    RVK:
    XA 36000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2012
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
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