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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We sincerely thanks to the funding support from each institution.
This research was supported by the Natural Science Foundation of Chongqing (cstc2022ycjh-bgzxm0145), the pilot program of Southwest University (SWU-XDZD22006).
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