State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, 639 Longmian Ave., Nanjing, Jiangsu Province, 211198, China.
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Kunlun Road, Nanjing, Jiangsu Province, 210009, China.
Cell Death Dis. 2023 Jun 7;14(6):350. doi: 10.1038/s41419-023-05877-y.
Pancreatic adenocarcinoma (PAAD) is the most malignant cancer with a high mortality rate. Despite the association of ribosomal protein L10 (RPL10) with PAAD and previous reports on RPL26 ufmylation, the relationship between RPL10 ufmylation and PAAD development remains unexplored. Here, we report the dissection of ufmylating process of RPL10 and potential roles of RPL10 ufmylation in PAAD development. The ufmylation of RPL10 was confirmed in both pancreatic patient tissues and cell lines, and specific modification sites were identified and verified. Phenotypically, RPL10 ufmylation significantly increased cell proliferation and stemness, which is principally resulted from higher expression of transcription factor KLF4. Moreover, the mutagenesis of ufmylation sites in RPL10 further demonstrated the connection of RPL10 ufmylation with cell proliferation and stemness. Collectively, this study reveals that PRL10 ufmylation plays an important role to enhance the stemness of pancreatic cancer cells for PAAD development.
胰腺导管腺癌（PAAD）是一种死亡率很高的恶性肿瘤。尽管核糖体蛋白 L10（RPL10）与 PAAD 有关，并且之前有报道称 RPL26 发生泛素样蛋白修饰，但 RPL10 泛素样蛋白修饰与 PAAD 发展之间的关系仍未被探索。在这里，我们报告了 RPL10 泛素化过程的剖析，以及 RPL10 泛素化在 PAAD 发展中的潜在作用。在胰腺患者组织和细胞系中均证实了 RPL10 的泛素化，并且鉴定和验证了特定的修饰位点。表型上，RPL10 泛素化显著增加了细胞增殖和干性，这主要是由于转录因子 KLF4 的表达水平升高所致。此外，RPL10 中泛素化位点的突变进一步证明了 RPL10 泛素化与细胞增殖和干性之间的联系。总之，这项研究揭示了 PRL10 泛素化在增强胰腺癌细胞干性以促进 PAAD 发展方面的重要作用。
