Asset Details
Do you wish to reserve the book?
SHP-2-upregulated ZEB1 is important for PDGFRα-driven glioma epithelial–mesenchymal transition and invasion in mice and humans
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
SHP-2-upregulated ZEB1 is important for PDGFRα-driven glioma epithelial–mesenchymal transition and invasion in mice and humans
Do you wish to request the book?
SHP-2-upregulated ZEB1 is important for PDGFRα-driven glioma epithelial–mesenchymal transition and invasion in mice and humans
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
SHP-2-upregulated ZEB1 is important for PDGFRα-driven glioma epithelial–mesenchymal transition and invasion in mice and humans
2016
Overview
Gliomas are highly malignant brain tumors that are highly invasive and resistant to conventional therapy. Receptor tyrosine kinases (RTKs) such as PDGFRα (platelet-derived growth factor receptor-α), which show frequent aberrant activation in gliomas, are associated with a process of epithelial–mesenchymal transition (EMT), a cellular alteration that confers a more invasive and drug-resistant phenotype. Although this phenomenon is well documented in human cancers, the processes by which RTKs including PDGFRα mediate EMT are largely unknown. Here, we report that SHP-2 (encoded by
PTPN11
) upregulates an EMT inducer, ZEB1, to mediate PDGFRα-driven glioma EMT, invasion and growth in glioma cell lines and patient-derived glioma stem cells (GSCs) using cell culture and orthotopic xenograft models. ZEB1 and activated PDGFRα were coexpressed in invasive regions of mouse glioma xenografts and clinical glioma specimens. Glioma patients with high levels of both phospho-PDGFRα (p-PDGFRα) and ZEB1 had significantly shorter overall survival compared with those with low expression of p-PDGFRα and ZEB1. Knockdown of ZEB1 inhibited PDGFA/PDGFRα-stimulated glioma EMT, tumor growth and invasion in glioma cell lines and patient-derived GSCs. PDGFRα mutant deficient of SHP2 binding (PDGFRα-F720) or phosphoinositide 3-kinase (PI3K) binding (PDGFRα-F731/42), knockdown of SHP2 or treatments of pharmacological inhibitor for PDGFRα-signaling effectors attenuated PDGFA/PDGFRα-stimulated ZEB1 expression, cell migration and GSC proliferation. Importantly, SHP-2 acts together with PI3K/AKT to regulate a ZEB1-miR-200 feedback loop in PDGFRα-driven gliomas. Taken together, our findings uncover a new pathway in which ZEB1 functions as a key regulator for PDGFRα-driven glioma EMT, invasiveness and growth, suggesting that ZEB1 is a promising therapeutic target for treating gliomas with high PDGFRα activation.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/109
/ 13/21
/ 13/44
/ 13/51
/ 13/89
/ 13/95
/ Animals
/ Brain Neoplasms - metabolism
/ Epithelial-Mesenchymal Transition - genetics
/ Humans
/ Medicine
/ Mice
/ Neoplastic Stem Cells - metabolism
/ Oncology
/ Original
/ Phosphatidylinositol 3-Kinases - metabolism
/ Protein Tyrosine Phosphatase, Non-Receptor Type 11 - genetics
/ Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism
/ Proto-Oncogene Proteins c-akt - metabolism
/ Receptor, Platelet-Derived Growth Factor alpha - genetics
/ Receptor, Platelet-Derived Growth Factor alpha - metabolism
