文章：

FBXO22通过RPS5/AKT/HIF-1α/VEGF-A信号轴促进肝细胞癌血管生成与转移

FBXO22 promotes HCC angiogenesis and metastasis via RPS5/AKT/HIF-1α/VEGF-A signaling axis 

原文发布日期：2025-01-15 

英文摘要：

The gene F-box only protein 22 (FBXO22) has been discovered to promote the development of liver cancer tumors. Nevertheless, there remains considerable ambiguity regarding the involvement of FBXO22 in the processes of angiogenesis and metastasis in hepatocellular carcinoma (HCC). Our study has confirmed a significant upregulation of FBXO22 expression in both HCC samples and cellular models. The increased level of FBXO22 correlates strongly with the number of tumors, presence of vascular invasion, and poor prognosis. Experimental investigations have shown that FBXO22 significantly enhances angiogenesis and metastasis of HCC both in vitro and in vivo. Mechanistically, FBXO22 interacts with and ubiquitinates 40S ribosomal protein S5 (RPS5) on Lys85, thereby promoting its K48-linked ubiquitin-mediated degradation in the cytoplasm. Following a decrease in the expression of RPS5, activation of downstream PI3K/AKT signaling pathway occurs, leading to elevated levels of HIF-1α and vascular endothelial growth factor A (VEGF-A). Our study has shown that FBXO22 facilitates HCC angiogenesis and metastasis via the RPS5/AKT/HIF-1α/VEGF-A signaling axis. Notably, inhibition of FBXO22 enhances the efficacy of Lenvatinib both in vitro and in vivo. Therefore, FBXO22 may present itself as a potential target for therapeutic intervention in the treatment of HCC. 

摘要翻译：

研究发现F-box only蛋白22（FBXO22）可促进肝癌肿瘤的发展。然而，FBXO22在肝细胞癌（HCC）血管生成和转移过程中的作用仍存在相当大的不确定性。我们的研究证实FBXO22在HCC样本和细胞模型中均呈现显著上调。FBXO22水平升高与肿瘤数量、血管侵犯及不良预后密切相关。实验研究表明，FBXO22在体外和体内均显著增强HCC的血管生成和转移能力。从机制上讲，FBXO22与40S核糖体蛋白S5（RPS5）相互作用，并在其Lys85位点进行泛素化修饰，从而促进其在细胞质中通过K48连锁泛素介导的降解。RPS5表达降低后，下游PI3K/AKT信号通路被激活，导致HIF-1α和血管内皮生长因子A（VEGF-A）水平升高。本研究揭示FBXO22通过RPS5/AKT/HIF-1α/VEGF-A信号轴促进HCC血管生成和转移。值得注意的是，抑制FBXO22可增强乐伐替尼在体外和体内的疗效。因此，FBXO22可能成为HCC治疗中具有潜力的干预靶点。

原文链接：

FBXO22 promotes HCC angiogenesis and metastasis via RPS5/AKT/HIF-1α/VEGF-A signaling axis