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01.09.2014 | Laboratory Investigation

A complex mechanism for HDGF-mediated cell growth, migration, invasion, and TMZ chemosensitivity in glioma

verfasst von: Ye Song, Zheng Hu, Hao Long, Yuping Peng, Xi’an Zhang, Tianshi Que, Shihao Zheng, Zhiyong Li, Gang Wang, Liu Yi, Zhen Liu, Weiyi Fang, Songtao Qi

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2014

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Abstract

HDGF is overexpressed in gliomas as compared to normal brain. We therefore analyzed the molecular mechanisms of HDGF action in gliomas. HDGF was downregulated in normal brain tissue as compared to glioma specimens at both the mRNA and the protein levels. In glioma samples, increased HDGF expression was associated with disease progression. Knocking down HDGF expression not only significantly decreased cellular proliferation, migration, invasion, and tumorigenesis, but also markedly enhanced TMZ-induced cytotoxicity and apoptosis in glioma cells. Mechanistic analyses revealed that CCND1, c-myc, and TGF-β were downregulated after stable HDGF knockdown in the U251 and U87 glioma cells. HDGF knockdown restored E-cadherin expression and suppressed mesenchymal cell markers such as vimentin, β-catenin, and N-cadherin. The expression of cleaved caspase-3 increased, while Bcl-2 decreased in each cell line following treatment with shHDGF and TMZ, as compared to TMZ alone. Furthermore, RNAi-based knockdown study revealed that HDGF is probably involved in the activation of both the PI3K/Akt and the TGF-β signaling pathways. Together, our data suggested that HDGF regulates glioma cell growth, apoptosis and epithelial–mesenchymal transition (EMT) probably through the Akt and the TGF-β signaling pathways. These results provide evidence that targeting HDGF or its downstream targets may lead to novel therapies for gliomas.

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Titel: A complex mechanism for HDGF-mediated cell growth, migration, invasion, and TMZ chemosensitivity in glioma
verfasst von: Ye Song
Zheng Hu
Hao Long
Yuping Peng
Xi’an Zhang
Tianshi Que
Shihao Zheng
Zhiyong Li
Gang Wang
Liu Yi
Zhen Liu
Weiyi Fang
Songtao Qi
Publikationsdatum: 01.09.2014
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 2/2014
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-014-1512-4

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