Yang Qi, Cao Chenhui, Wu Binghuo, Yang Haochi, Tan Tian, Shang Dan, Xu Chuan, Huang Xiaoyi
Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin 150001, China.
Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Cancers (Basel). 2024 Jan 30;16(3):590. doi: 10.3390/cancers16030590.
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.
在我们之前的研究中，通过促进DNA同源重组修复，PPIP5K2已被证明对提高结直肠癌生存率至关重要。然而，它在非小细胞肺癌（NSCLC）肿瘤发生中的作用仍然未知，NSCLC是全球最常见的癌症及癌症相关死亡的主要原因。在此，我们最初通过体外和体内的功能丧失和功能获得实验发现，PPIP5K2对NSCLC细胞的增殖有显著影响。此外，PPIP5K2能够以EMT依赖的方式调节NSCLC细胞的转移。在机制探索方面，我们发现敲低PPIP5K2可显著抑制AKT/mTOR信号通路的磷酸化，而PPIP5K2的过表达则产生相反的效果。通过使用AKT信号相关激动剂或拮抗剂，我们进一步证明PPIP5K2部分通过AKT/mTOR途径调节NSCLC的肿瘤发生。总之，PPIP5K2通过激活AKT/mTOR信号轴在NSCLC中发挥关键的致癌作用。预计靶向PPIP5K2可能成为NSCLC患者一种可行的治疗方法。
