文章：

Rabenosyn-5通过抑制CDC42活性抑制非小细胞肺癌转移

Rabenosyn-5 suppresses non-small cell lung cancer metastasis via inhibiting CDC42 activity 

原文发布日期：2024-07-29 

英文摘要：

Metastasis, the primary cause of death in lung cancer patients, is facilitated by cytoskeleton remodeling, which plays a crucial role in cancer cell migration and invasion. However, the precise regulatory mechanisms of intracellular trafficking proteins involved in cytoskeleton remodeling remain unclear. In this study, we have identified Rabenosyn-5 (Rbsn) as an inhibitor of filopodia formation and lung cancer metastasis. Mechanistically, Rbsn interacts with CDC42 and functions as a GTPase activating protein (GAP), thereby inhibiting CDC42 activity and subsequent filopodia formation. Furthermore, we have discovered that Akt phosphorylates Rbsn at the Thr253 site, and this phosphorylation negates the inhibitory effect of Rbsn on CDC42 activity. Additionally, our analysis reveals that Rbsn expression is significantly downregulated in lung cancer, and this decrease is associated with a worse prognosis. These findings provide strong evidence supporting the role of Rbsn in suppressing lung cancer progression through the inhibition of metastasis. 

摘要翻译：

转移是肺癌患者死亡的主要原因，而细胞骨架重塑在这一过程中起关键作用，它促进癌细胞的迁移和侵袭。然而，细胞骨架重塑中细胞内运输蛋白的精确调控机制尚不明确。本研究首次发现Rabenosyn-5（Rbsn）能抑制伪足形成和肺癌转移。从机制上讲，Rbsn与CDC42相互作用，发挥GTP酶激活蛋白（GAP）功能，从而抑制CDC42活性及后续伪足形成。此外，我们发现Akt激酶能使Rbsn的Thr253位点发生磷酸化，该磷酸化修饰会解除Rbsn对CDC42活性的抑制作用。临床数据分析进一步显示，Rbsn在肺癌组织中表达显著下调，且其低表达与患者不良预后密切相关。这些发现为Rbsn通过抑制转移来阻遏肺癌进展的作用提供了有力证据。

原文链接：

Rabenosyn-5 suppresses non-small cell lung cancer metastasis via inhibiting CDC42 activity