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Cytoskeleton-associated protein 4 (CKAP4) promotes malignant progression of human gliomas through inhibition of the Hippo signaling pathway

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

Gliomas are the most common and aggressive malignant brain tumors and are associated with high mortality and incidence in humans. Despite rigorous multi-modal therapy, including surgery, chemotherapy and radiotherapy, patients with malignant glioma survive an average of 12–15 months following primary diagnosis. Therefore, new molecular biomarkers are urgently needed for diagnosis and targeted therapy. Here, we find that suppression of CKAP4 might inhibit glioma growth through regulation of Hippo signaling.

Methods

We examined the expression levels of CKAP4 through analysis of RNA sequencing data from GEPIA and CGGA databases. Then, Lentivirus was used to construct stable cell lines with knockout or overexpression of CKAP4. Next, the function of CKAP4 on glioma was investigated in vitro and in an orthotopic brain tumor model in mice. Lastly, luciferase reporter assay, immunofluorescence and immunoblotting were performed to explore the potential mechanism of how CKAP4 affects gliomas.

Results

CKAP4 is highly upregulated in glioma and high CKAP4 expressing tumors were associated with poor patient survival. And CKAP4 promotes malignant progression of gliomas via inhibiting Hippo signaling.

Conclusion

CKAP4 has potential as a promising biomarker and can predict the prognosis of patients with gliomas. And targeting CKAP4 expression may be an effective therapeutic strategy for the treatment of human gliomas.

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Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available due to the risk of compromising individual privacy but are available from the corresponding author on reasonable request and provided that an appropriate collaboration agreement can be agreed upon.

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Funding

This work was supported by the National Natural Science Foundation of China (81903126 and 81972351), the Special Foundation for Taishan Scholars (ts20110184, tshw201502056, tsqn201909173 and tsqn20161067), the Department of Science & Technology of Shandong Province (ZR2019ZD33), the China Postdoctoral Science Foundation (2018M642666 and 2020T130371), the Jinan Science and Technology Bureau of Shandong Province (2019GXRC006), the 111 Project (B20058), the Shandong research institute of industrial technology.

Author information

Author notes

  1. Jian Wang and Xingang Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Cheeloo College of Medicine, Shandong University, 107# Wenhua Xi Road, Shandong, 250012, Jinan, China

    Tao Luo, Kaikai Ding, Jianxiong Ji, Xin Zhang, Xiaobing Yang, Anjing Chen, Bin Huang, Di Zhang, Jian Wang & Xingang Li

  2. Key Laboratory of Brain Functional Remodeling, Shandong, 250012, Jinan, China

    Tao Luo, Kaikai Ding, Jianxiong Ji, Xin Zhang, Xiaobing Yang, Anjing Chen, Bin Huang, Di Zhang, Jian Wang & Xingang Li

  3. School of Medicine, Shandong University, Shandong, China

    Anjing Chen

  4. Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009, Bergen, Norway

    Jian Wang

  5. Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling, 107# Wenhua Xi Road, Shandong, 250012, Jinan, China

    Jian Wang & Xingang Li

Authors
  1. Tao Luo
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Contributions

All authors contributed to the study conception and design. TL, JW, and XL conceived and designed the project. TL, KD, JJ, XZ, XY performed experiments. TL, KD, JJ analyzed the data. TL, KD, JJ wrote the manuscript. AC, BH, DZ provided reagents and materials. JW, and XL supervised the study.

Corresponding author

Correspondence to Xingang Li.

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Conflict of interest

All co-authors declare no potential conflicts of interest.

Ethics approval and consent to participate

The protocols in the present study involving human samples were approved by the Research Ethics Committee of Shandong University (Shandong, China), and the study was conducted in accordance with the Declaration of Helsinki. The animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of Shandong University and performed under the guidance of the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All participants in the study provided written informed consent.

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Written informed consent for publication of their clinical details was obtained from the relative of the patient. A copy of the consent form is available for review by the Editor of this journal.

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Luo, T., Ding, K., Ji, J. et al. Cytoskeleton-associated protein 4 (CKAP4) promotes malignant progression of human gliomas through inhibition of the Hippo signaling pathway. J Neurooncol 154, 275–283 (2021). https://doi.org/10.1007/s11060-021-03831-6

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