RRM2 promotes liver metastasis of pancreatic cancer by stabilizing YBX1 and activating the TGF-beta pathway

作者：Zhouyuan Du, Qun Zhang, Xingxing Xiang, Wei Li, Qinglin Yang, Haixin Yu, Tao Liu · 发表于：iScience · 年份：2024 · DOI：10.1016/j.isci.2024.110864 · 被引用次数：7 · 研究领域：RNA modifications and cancer、Metal-Catalyzed Oxygenation Mechanisms、Ferroptosis and cancer prognosis

Pancreatic cancer is one of the most malignant types of cancer, and despite recent advances in treatment, prognosis remains extremely poor. The most common site of pancreatic cancer metastasis is the liver. Elucidating the molecular mechanisms of pancreatic cancer progression and liver metastasis is essential for improving patients' survival. Ribonucleotide reductase subunit M2 (RRM2) has been linked to many types of cancers and is associated with tumor progression. However, the role of RRM2 in the liver metastasis of pancreatic cancer is still unclear. In this study, RRM2 was found to promote the malignant biological behavior of pancreatic cancer and enhance its liver metastasis. Further studies on the downstream molecular mechanisms of RRM2 revealed that RRM2 stabilizes YBX1, upregulates TGFBR1, and activates the TGF-beta pathway to promote pancreatic cancer progression and liver metastasis. In summary, these results suggest that RRM2 may be an effective therapeutic target for pancreatic cancer liver metastasis.