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AKIP1 accelerates glioblastoma progression through stabilizing EGFR expression

Oncogene volume 42, pages 2905–2918 (2023)Cite this article

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Abstract

A Kinase Interacting Protein 1 (AKIP1) is found to be overexpressed in a variety of human cancers and associated with patients’ worse prognosis. Several studies have established AKIP1’s malignant functions in tumor metastasis, angiogenesis, and chemoradiotherapy resistance. However, the mechanism of AKIP1 involved in accelerating glioblastoma (GBM) progression remains unknown. Here, we showed that the expression of AKIP1 was positively correlated with the glioma pathological grades. Down-regulating AKIP1 greatly impaired the proliferation, colony formation, and tumorigenicity of GBM cells. In terms of the mechanism, AKIP1 cooperates with transcriptional factor Yin Yang 1 (YY1)-mediated Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) transcriptional activation, enhancing the stability of Epidermal Growth Factor Receptor (EGFR). YY1 was identified as a potential transcriptional factor of HSP90AA1 and directly interacts with AKIP1. The overexpression of HSP90α significantly reversed AKIP1 depletion incurred EGFR instability and the blocked cell proliferation. Moreover, we further investigated the interacted pattern between EGFR and HSP90α. These findings established that AKIP1 acted as a critical oncogenic factor in GBM and uncovered a novel regulatory mechanism in EGFR aberrant expression.

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Fig. 1: AKIP1 is essential for glioma progression and associated with patients’ poor prognosis.
Fig. 2: AKIP1 is required for proliferation and tumorigenicity of GBM cell.
Fig. 3: AKIP1 regulates the stability of EGFR by impacting its PTM.
Fig. 4: AKIP1 affects EGFR stability by regulating HSP90AA1 transcription.
Fig. 5: The interaction between EGFR and HSP90α.
Fig. 6: AKIP1 and YY1 cooperate to regulate HSP90AA1 transcriptional activation.
Fig. 7: AKIP1 affects the intracranial tumorigenicity of GBM cells.

Data availability

All the data and materials in the current study are available and can be requested from the corresponding author, HC.

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Acknowledgements

We sincerely thanks to the funding support from each institution.

Funding

This research was supported by the Natural Science Foundation of Chongqing (cstc2022ycjh-bgzxm0145), the pilot program of Southwest University (SWU-XDZD22006).

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Author notes

  1. These authors contributed equally: Sicheng Wan, Chaolong Liu, Chongyang Li.

Authors and Affiliations

  1. State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing, 400716, China

    Sicheng Wan, Chaolong Liu, Zhi Wang, Gaichao Zhao, Jingui Li, Wenhao Ran, Xi Zhong, Yongsen Li & Hongjuan Cui

  2. Jinfeng Laboratory, Chongqing, 401329, China

    Sicheng Wan, Chaolong Liu, Zhi Wang, Gaichao Zhao, Jingui Li, Wenhao Ran, Xi Zhong, Yongsen Li & Hongjuan Cui

  3. Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, 400715, China

    Sicheng Wan, Chaolong Liu, Zhi Wang, Gaichao Zhao, Jingui Li, Wenhao Ran, Xi Zhong, Yongsen Li & Hongjuan Cui

  4. Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China

    Sicheng Wan, Chaolong Liu, Zhi Wang, Gaichao Zhao, Jingui Li, Wenhao Ran, Xi Zhong, Yongsen Li & Hongjuan Cui

  5. School of Basic Medicine, Fudan University, Shanghai, 200032, China

    Chongyang Li

  6. Department of Radiology and Nuclear Medicine, The First Hospital of HeBei Medical University, Shijiazhuang, HeBei Province, 050000, China

    Li Zhang

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Contributions

HC and LZ supervised this research; SW, CL, CL, ZW, WR, JL, GZ, XZ, and YL performed the research; SW designed the outlines of this research and wrote the manuscript. ZW reviewed and revised the manuscript.

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Correspondence to Li Zhang or Hongjuan Cui.

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The authors declare no competing interests.

Ethics approval and consent to participate

All animal experiments were supervised and approved by the Committee of Animal Protection and Ethics of Southwest University. Experiments involved in glioma patients’ samples were obtained from BioAitech (Xian, China) and the studies were approved by the Ethics Committee of Southwest University and the Affiliated Hospital of Southwest University (The Ninth People’s Hospital of Chongqing). All patients and their relatives were informed and consented this study.

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Wan, S., Liu, C., Li, C. et al. AKIP1 accelerates glioblastoma progression through stabilizing EGFR expression. Oncogene 42, 2905–2918 (2023). https://doi.org/10.1038/s41388-023-02796-2

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