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

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A Correction to this article was published on 01 September 2020

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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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  • 08 October 2020

    In the original publication, there are errors in Fig.��3D and Fig.��5C and are corrected as follows.

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Acknowledgments

This study was supported by National Nature Science Fund of China (No. 81372692) (http://www.nsfc.gov.cn), Natural Science Fund of Guangdong Province (No. S2013010014886) (http://www.gdstc.gov.cn), Medical Scientific Research Fund of Guangdong Province (No. B2013238) (http://www.medste.gd.cn), Scientific Research initiative Project Fund of Southern Medical University (No. B1012032) (http://www.fimmu.com) and President Fund of Nanfang Hospital (2011C007, 2012C011) (http://www.nfyy.com). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors have declared that no conflict of interest exist.

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Authors and Affiliations

  1. Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China

    Ye Song, Zheng Hu, Hao Long, Yuping Peng, Xi’an Zhang, Tianshi Que, Shihao Zheng, Zhiyong Li, Gang Wang, Liu Yi & Songtao Qi

  2. Cancer Research Institute of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China

    Ye Song, Zhen Liu & Weiyi Fang

  3. Department of Pathology, Basic School of Guangzhou Medical College, Guangzhou, Guangdong, People’s Republic of China

    Zhen Liu

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  1. Ye Song
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Correspondence to Zhen Liu, Weiyi Fang or Songtao Qi.

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Ye Song, Zheng Hu and Hao Long have contributed equally to this work.

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Song, Y., Hu, Z., Long, H. et al. A complex mechanism for HDGF-mediated cell growth, migration, invasion, and TMZ chemosensitivity in glioma. J Neurooncol 119, 285–295 (2014). https://doi.org/10.1007/s11060-014-1512-4

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