RRM2通过稳定YBX1并激活转化生长因子-β（TGF-β）信号通路促进胰腺癌肝转移。

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

作者信息

Du Zhouyuan, Zhang Qun, Xiang Xingxing, Li Wei, Yang Qinglin, Yu Haixin, Liu Tao

机构信息

Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

iScience. 2024 Aug 31;27(10):110864. doi: 10.1016/j.isci.2024.110864. eCollection 2024 Oct 18.

DOI:10.1016/j.isci.2024.110864

PMID:39398252

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11470400/

Abstract

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.

摘要

胰腺癌是最恶性的癌症类型之一，尽管近期治疗取得了进展，但预后仍然极差。胰腺癌转移最常见的部位是肝脏。阐明胰腺癌进展和肝转移的分子机制对于提高患者生存率至关重要。核糖核苷酸还原酶亚基M2（RRM2）与多种癌症相关，并与肿瘤进展有关。然而，RRM2在胰腺癌肝转移中的作用仍不清楚。在本研究中，发现RRM2促进胰腺癌的恶性生物学行为并增强其肝转移。对RRM2下游分子机制的进一步研究表明，RRM2使YBX1稳定，上调TGFBR1，并激活TGF-β途径以促进胰腺癌进展和肝转移。总之，这些结果表明RRM2可能是胰腺癌肝转移的有效治疗靶点。