文章：

CDK4/6-USP51轴通过ZEB1调控肺腺癌转移

CDK4/6-USP51 axis regulates lung adenocarcinoma metastasis through ZEB1 

原文发布日期：2022-01-20 

英文摘要：

USP51 is a member of the deubiquitinase (DUB) family that participates in many pathophysiological processes. However, the aberrant expression and biological function of USP51 in cancer progression remain largely unclear. In this study, we demonstrated that USP51 is overexpressed in metastatic human lung adenocarcinoma and patients with high USP51 expression in their tumors have shorter overall survival than those with low expression of USP51. Moreover, we showed that USP51 promotes tumor metastasis and invasion through regulating ZEB1, which is a key transcriptional factor that induces the malignant progression of lung adenocarcinoma. In terms of molecular mechanism, USP51 is phosphorylated and activated by CDK4/6, thus resulting in the deubiquitination and stabilization of ZEB1 protein. Of note, we also confirmed that the expression of p-RB (an indicator of CDK4/6 activity), p-USP51 and ZEB1 are significantly positively correlated in human lung adenocarcinoma samples. In conclusion, these findings revealed that the CDK4/6-USP51-ZEB1 signaling pathway is a driver of lung adenocarcinoma metastasis, which could be a potential therapeutic strategy for the treatment of malignant tumors. 

摘要翻译： 

USP51是去泛素化酶（DUB）家族成员，参与多种病理生理过程。然而，USP51在癌症进展中的异常表达和生物学功能仍 largely 不明确。本研究表明，USP51在转移性人肺腺癌中过度表达，且肿瘤中USP51高表达患者的总生存期较短表达患者更短。此外，我们发现USP51通过调控ZEB1（诱导肺腺癌恶性进展的关键转录因子）促进肿瘤转移和侵袭。在分子机制层面，USP51被CDK4/6磷酸化并激活，从而导致ZEB1蛋白的去泛素化和稳定化。值得注意的是，我们还在人肺腺癌样本中证实p-RB（CDK4/6活性指标）、p-USP51与ZEB1表达呈显著正相关。综上所述，这些发现揭示了CDK4/6-USP51-ZEB1信号通路是肺腺癌转移的驱动因素，可能成为治疗恶性肿瘤的潜在策略。

原文链接：

CDK4/6-USP51 axis regulates lung adenocarcinoma metastasis through ZEB1