Rab11a promotes proliferation and invasion through regulation of YAP in non-small cell lung cancer.
Rab11a promotes proliferation and invasion through regulation of YAP in non-small cell lung cancer.
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Rab11a 通过调节 YAP 促进非小细胞肺癌增殖和侵袭
DOI：
10.18632/oncotarget.15359
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发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Wang E
中科院分区：
文献类型：
--
作者：
Dong Q;Fu L;Zhao Y;Du Y;Li Q;Qiu X;Wang E
Rab11a是一种进化上保守的Rab GTP酶，在细胞内转运中发挥重要作用，并与肿瘤的进展有关。然而，它在人类非小细胞肺癌(NSCLC)中的作用尚未被探讨。在本研究中，我们发现Rab11a蛋白在57/122例非小细胞肺癌组织中表达上调。Rab11a过表达与晚期TNM分期、阳性淋巴结状态及患者预后不良有关。Rab11a过表达促进了NSCLC细胞的增殖、集落形成、侵袭和迁移，上调了细胞周期蛋白D1和E的表达，下调了p27的表达。裸鼠移植瘤实验表明，Rab11a促进了体内肿瘤的生长。重要的是，我们发现Rab11a诱导YAP蛋白并抑制Hippo信号转导。去YAP后，Rab11a对细胞周期蛋白和细胞增殖的影响消失。进一步的免疫沉淀实验表明，Rab11a与YAP在肺癌细胞中相互作用。综上所述，本研究提示Rab11a在非小细胞肺癌中可能是一种重要的癌蛋白和YAP的调节因子。
Rab11a, an evolutionarily conserved Rab GTPases, plays important roles in intracellular transport and has been implicated in cancer progression. However, its role in human non-small cell lung cancer (NSCLC) has not been explored yet. In this study, we discovered that Rab11a protein was upregulated in 57/122 NSCLC tissues. Rab11a overexpression associated with advanced TNM stage, positive nodal status and poor patient prognosis. Rab11a overexpression promoted proliferation, colony formation, invasion and migration with upregulation of cyclin D1, cyclin E, and downregulation of p27 in NSCLC cell lines. Nude mice xenograft demonstrated that Rab11a promoted in vivo cancer growth. Importantly, we found that Rab11a induced YAP protein and inhibited Hippo signaling. Depletion of YAP abolished the effects of Rab11a on cell cycle proteins and cell proliferation. Furthermore, immunoprecipitation showed that Rab11a interacted with YAP in lung cancer cells. In conclusion, the present study suggestes that Rab11a serves as an important oncoprotein and a regulator of YAP in NSCLC.