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01-12-2017 | Laboratory Investigation

SHP2 regulates proliferation and tumorigenicity of glioma stem cells

Authors: Laura Roccograndi, Zev A. Binder, Logan Zhang, Nicola Aceto, Zhuo Zhang, Mohamed Bentires-Alj, Ichiro Nakano, Nadia Dahmane, Donald M. O’Rourke

Published in: Journal of Neuro-Oncology | Issue 3/2017

Abstract

SHP2 is a cytoplasmic protein tyrosine phosphatase (PTPase) involved in multiple signaling pathways and was the first identified proto-oncogene PTPase. Previous work in glioblastoma (GBM) has demonstrated the role of SHP2 PTPase activity in modulating the oncogenic phenotype of adherent GBM cell lines. Mutations in PTPN11, the gene encoding SHP2, have been identified with increasing frequency in GBM. Given the importance of SHP2 in developing neural stem cells, and the importance of glioma stem cells (GSCs) in GBM oncogenesis, we explored the functional role of SHP2 in GSCs. Using paired differentiated and stem cell primary cultures, we investigated the association of SHP2 expression with the tumor stem cell compartment. Proliferation and soft agar assays were used to demonstrate the functional contribution of SHP2 to cell growth and transformation. SHP2 expression correlated with SOX2 expression in GSC lines and was decreased in differentiated cells. Forced differentiation of GSCs by removal of growth factors, as confirmed by loss of SOX2 expression, also resulted in decreased SHP2 expression. Lentiviral-mediated knockdown of SHP2 inhibited proliferation. Finally, growth in soft-agar was similarly inhibited by loss of SHP2 expression. Our results show that SHP2 function is required for cell growth and transformation of the GSC compartment in GBM.

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Title: SHP2 regulates proliferation and tumorigenicity of glioma stem cells
Authors: Laura Roccograndi
Zev A. Binder
Logan Zhang
Nicola Aceto
Zhuo Zhang
Mohamed Bentires-Alj
Ichiro Nakano
Nadia Dahmane
Donald M. O’Rourke
Publication date: 01-12-2017
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 3/2017
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-017-2610-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

SHP2 regulates proliferation and tumorigenicity of glioma stem cells

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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