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Cathepsin B and uPAR regulate self-renewal of glioma-initiating cells through GLI-regulated Sox2 and Bmi1 expression.
Gopinath, Sreelatha; Malla, Ramarao; Alapati, Kiranmai; Gorantla, Bharathi; Gujrati, Meena; Dinh, Dzung H; Rao, Jasti S.
Afiliação
  • Gopinath S; Department of Cancer Biology & Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61656, USA.
Carcinogenesis ; 34(3): 550-9, 2013 Mar.
Article em En | MEDLINE | ID: mdl-23222817
ABSTRACT
Cancer-initiating cells comprise a heterogeneous population of undifferentiated cells with the capacity for self-renewal and high proliferative potential. We investigated the role of uPAR and cathepsin B in the maintenance of stem cell nature in glioma-initiating cells (GICs). Simultaneous knockdown of uPAR and cathepsin B significantly reduced the expression of CD133, Nestin, Sox2 and Bmi1 at the protein level and GLI1 and GLI2 at the messenger RNA level. Also, knockdown of uPAR and cathepsin B resulted in a reduction in the number of GICs as well as sphere size. These changes are mediated by Sox2 and Bmi1, downstream of hedgehog signaling. Addition of cyclopamine reduced the expression of Sox2 and Bmi1 along with GLI1 and GLI2 expression, induced differentiation and reduced subsphere formation of GICs thereby indicating that hedgehog signaling acts upstream of Sox2 and Bmi1. Further confirmation was obtained from increased luciferase expression under the control of a GLI-bound Sox2 and Bmi1 luciferase promoter. Simultaneous knockdown of uPAR and cathepsin B also reduced the expression of Nestin Sox2 and Bmi1 in vivo. Thus, our study highlights the importance of uPAR and cathepsin B in the regulation of malignant stem cell self-renewal through hedgehog components, Bmi1 and Sox2.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Células-Tronco Neoplásicas / Catepsina B / Fatores de Transcrição SOXB1 / Receptores de Ativador de Plasminogênio Tipo Uroquinase / Complexo Repressor Polycomb 1 / Glioma Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Células-Tronco Neoplásicas / Catepsina B / Fatores de Transcrição SOXB1 / Receptores de Ativador de Plasminogênio Tipo Uroquinase / Complexo Repressor Polycomb 1 / Glioma Idioma: En Ano de publicação: 2013 Tipo de documento: Article