发现一种名为激酶相互作用蛋白1（AKIP1）的蛋白在多种人类肿瘤中过表达，并与患者的不良预后相关。多项研究证实AKIP1在肿瘤转移、血管生成和化疗放疗耐药中的恶性功能。然而，AKIP1在加速胶质母细胞瘤（GBM）进展中的作用机制还不清楚。本研究显示AKIP1的表达与胶质瘤的病理分级呈正相关。下调AKIP1显著抑制GBM细胞的增殖、集落形成能力和肿瘤形成能力。在机制方面，AKIP1与转录因子Yin Yang 1 (YY1)介导的热休克蛋白90α家族A类成员1（HSP90AA1）转录活化合作，增强表皮生长因子受体（EGFR）的稳定性。YY1被确定为HSP90AA1的一个潜在转录因子，并直接与AKIP1相互作用。α HSP90的过表达显著逆转了AKIP1的消耗引起的EGFR不稳定和细胞增殖受阻。此外，我们进一步研究了EGFR和HSP90α之间的相互作用模式。这些发现确立了AKIP1在GBM中的关键致癌因子作用，并揭示了EGFR异常表达的新的调节机制。© 2023. 作者，独家许可给Springer Nature 有限公司。

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.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.