Through facilitating DNA homologous recombination repair, PPIP5K2 has been proven to be essential for improving colorectal cancer survival in our previous research. However, its function in the tumorigenesis of NSCLC, the most common cancer and the primary cause of cancer-related death globally, is still unknown. Here, we initially discovered that PPIP5K2 had significant effects on proliferation of NSCLC cells through loss- and gain-of-function assays in vitro and in vivo. Moreover, PPIP5K2 is capable of regulating NSCLC cells metastasis in an EMT-dependent manner. In terms of mechanism exploration, we found that PPIP5K2 knockdown can significantly inhibit the phosphorylation of AKT/mTOR signaling pathway, whereas the overexpression of PPIP5K2 resulted in converse effects. By employing AKT signaling related agonists or antagonists, we further demonstrated that PPIP5K2 regulates NSCLC tumorigenesis partly via the AKT/mTOR pathway. In conclusion, PPIP5K2 plays a key oncogenic role in NSCLC by the activation of the AKT/mTOR signaling axis. It is anticipated that targeting PPIP5K2 might emerge as a viable therapeutic approach for NSCLC patients.
通过促进DNA同源重组修复，PPIP5K2已被证实对提高结直肠癌患者生存率至关重要，这在我们先前的研究中已得到验证。然而，其在全球最常见且导致癌症相关死亡的首要原因——非小细胞肺癌（NSCLC）的肿瘤发生过程中的功能仍属未知。本研究首次通过体外及体内的功能缺失与功能获得实验发现，PPIP5K2对NSCLC细胞的增殖具有显著影响。此外，PPIP5K2能够以EMT依赖的方式调控NSCLC细胞的转移。在机制探索层面，我们发现敲低PPIP5K2可显著抑制AKT/mTOR信号通路的磷酸化，而过表达PPIP5K2则产生相反效应。通过使用AKT信号相关激动剂或拮抗剂，我们进一步证实PPIP5K2部分通过AKT/mTOR通路调控NSCLC的肿瘤发生。综上所述，PPIP5K2通过激活AKT/mTOR信号轴在NSCLC中发挥关键致癌作用。靶向PPIP5K2有望成为NSCLC患者潜在可行的治疗策略。
肿瘤(癌症)患者之家