Overexpression of A‐kinase‐interacting protein 1 (AKIP1) has been reported in prostate and breast cancers. Nevertheless, the clinical potential of AKIP1 during the development of cervical cancer (CC) remains unclear. A series of experiments involving BdU, colony formation, wound healing and cell invasion assays were performed to determine cell proliferation, migration and invasion, respectively. Gene expression changes were validated by qRT‐PCR, Western blotting and immunocytochemistry. We found that AKIP1 expression is increased in CC cell lines and tissue specimens from CC patients. The elevated AKIP1 expression in primary tumours was related to lymph node metastasis in CC patients. In addition, we observed that overexpression of AKIP1 promotes CC cell proliferation. Enhanced expression of AKIP1 facilitated the migration and invasion of CC cells by inducing NF‐κB‐dependent epithelial‐mesenchymal transition (EMT). Moreover, mechanistic investigations revealed that AKIP1 induced nuclear translocation and phosphorylation of the p65 NF‐κB subunit through the PI3K/Akt/IKKβ pathway. Conversely, enhanced expression of phosphatase and tensin homologue (PTEN) inhibited this signalling pathway and restored an epithelial phenotype to CC cells in the presence of overexpressed AKIP1. Our results indicate that AKIP1 promotes the EMT and metastasis in CC by activating NF‐κB signalling through the PI3K/Akt/IKKβ pathway, suggesting that AKIP1 could be a pivotal regulator of an EMT axis in CC.

中文翻译：

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A激酶相互作用蛋白1通过PI3K / Akt /IKKβ途径促进宫颈癌的EMT和转移。

据报道在前列腺癌和乳腺癌中过表达A激酶相互作用蛋白1（AKIP1）。尽管如此，AKIP1在宫颈癌（CC）发生过程中的临床潜力仍不清楚。进行了一系列涉及BdU，集落形成，伤口愈合和细胞侵袭测定的实验，分别测定细胞增殖，迁移和侵袭。基因表达的变化通过qRT-PCR，蛋白质印迹和免疫细胞化学验证。我们发现，AKIP1表达在CC细胞系和CC患者的组织标本中增加。CC患者的原发性肿瘤中AKIP1表达升高与淋巴结转移有关。此外，我们观察到AKIP1的过表达促进CC细胞增殖。AKIP1的增强表达通过诱导NF-κB依赖性上皮-间质转化（EMT）促进CC细胞的迁移和侵袭。此外，机理研究表明，AKIP1通过PI3K / Akt /IKKβ途径诱导p65NF-κB亚基的核易位和磷酸化。相反，在过表达的AKIP1的存在下，磷酸酶和张力蛋白同源物（PTEN）的表达增加抑制了该信号传导途径并恢复了CC细胞的上皮表型。我们的结果表明，AKIP1通过激活PI3K / Akt /IKKβ途径的NF-κB信号传导，促进CC中的EMT和转移，提示AKIP1可能是CC中EMT轴的关键调节剂。机理研究表明，AKIP1通过PI3K / Akt /IKKβ途径诱导p65NF-κB亚基的核易位和磷酸化。相反，在过表达的AKIP1的存在下，磷酸酶和张力蛋白同源物（PTEN）的表达增加抑制了该信号传导途径并恢复了CC细胞的上皮表型。我们的结果表明，AKIP1通过激活PI3K / Akt /IKKβ途径的NF-κB信号传导，促进CC中的EMT和转移，这表明AKIP1可能是CC中EMT轴的关键调节剂。机理研究表明，AKIP1通过PI3K / Akt /IKKβ途径诱导p65NF-κB亚基的核易位和磷酸化。相反，在过量表达的AKIP1的存在下，磷酸酶和张力蛋白同源物（PTEN）的表达增加抑制了该信号传导途径并恢复了CC细胞的上皮表型。我们的结果表明，AKIP1通过激活PI3K / Akt /IKKβ途径的NF-κB信号传导，促进CC中的EMT和转移，提示AKIP1可能是CC中EMT轴的关键调节剂。