Rabenosyn-5 通过抑制 CDC42 活性来抑制非小细胞肺癌转移。
Rabenosyn-5 suppresses non-small cell lung cancer metastasis via inhibiting CDC42 activity.
发表日期：2024 Jul 29
作者：
Xiong Guo, Bin Mu, Lin Zhu, Yanli Zhuo, Ping Mu, Fu Ren, Fangjin Lu
来源：
CANCER GENE THERAPY
摘要：
转移是肺癌患者死亡的主要原因，细胞骨架重塑促进了转移，细胞骨架重塑在癌细胞迁移和侵袭中发挥着至关重要的作用。然而，参与细胞骨架重塑的细胞内运输蛋白的精确调节机制仍不清楚。在这项研究中，我们发现 Rabenosyn-5 (Rbsn) 是丝状伪足形成和肺癌转移的抑制剂。从机制上讲，Rbsn 与 CDC42 相互作用并作为 GTP 酶激活蛋白 (GAP) 发挥作用，从而抑制 CDC42 活性和随后的丝状伪足形成。此外，我们发现Akt在Thr253位点磷酸化Rbsn，这种磷酸化抵消了Rbsn对CDC42活性的抑制作用。此外，我们的分析表明，Rbsn 表达在肺癌中显着下调，并且这种下降与较差的预后相关。这些发现提供了强有力的证据，支持 Rbsn 通过抑制转移来抑制肺癌进展的作用。© 2024。作者。
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.© 2024. The Author(s).