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Phage display targeting identifies EYA1 as a regulator of glioblastoma stem cell maintenance and proliferation.
Kim, JongMyung; She, Chunhua; Potez, Marine; Huang, Ping; Wu, Qiulian; Prager, Briana C; Qiu, Zhixin; Bao, Shideng; Rich, Jeremy N; Liu, James K C.
Afiliação
  • Kim J; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
  • She C; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
  • Potez M; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
  • Huang P; Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
  • Wu Q; Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, California, USA.
  • Prager BC; Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, California, USA.
  • Qiu Z; Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, California, USA.
  • Bao S; Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
  • Rich JN; Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, California, USA.
  • Liu JKC; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Stem Cells ; 39(7): 853-865, 2021 07.
Article em En | MEDLINE | ID: mdl-33594762
Glioblastoma (GBM) ranks among the most lethal of human malignancies with GBM stem cells (GSCs) that contribute to tumor growth and therapeutic resistance. Identification and isolation of GSCs continue to be a challenge, as definitive methods to purify these cells for study or targeting are lacking. Here, we leveraged orthogonal in vitro and in vivo phage display biopanning strategies to isolate a single peptide with GSC-specific binding properties. In silico analysis of this peptide led to the isolation of EYA1 (Eyes Absent 1), a tyrosine phosphatase and transcriptional coactivator. Validating the phage discovery methods, EYA1 was preferentially expressed in GSCs compared to differentiated tumor progeny. MYC is a central mediator of GSC maintenance but has been resistant to direct targeting strategies. Based on correlation and colocalization of EYA1 and MYC, we interrogated a possible interaction, revealing binding of EYA1 to MYC and loss of MYC expression upon targeting EYA1. Supporting a functional role for EYA1, targeting EYA1 expression decreased GSC proliferation, migration, and self-renewal in vitro and tumor growth in vivo. Collectively, our results suggest that phage display can identify novel therapeutic targets in stem-like tumor cells and that an EYA1-MYC axis represents a potential therapeutic paradigm for GBM.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bacteriófagos / Neoplasias Encefálicas / Glioblastoma Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bacteriófagos / Neoplasias Encefálicas / Glioblastoma Idioma: En Ano de publicação: 2021 Tipo de documento: Article