Knockdown Rab11-FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling
Knockdown Rab11-FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling
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敲低 Rab11-FIP2 通过抑制 Rho GTPase 信号传导抑制鼻咽癌的迁移和侵袭
DOI：
10.1002/jcb.29344
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发表时间：
2019-08-26
影响因子：
4
通讯作者：
Xiao, Xue
中科院分区：
文献类型：
--
作者：
Feng, Guofei;Qin, Liting;Xiao, Xue
Rab11家族相互作用蛋白2 （Rab11- fip2）是Rab11小GTPase的保守蛋白和效应分子。Rab11- fip2通过与Rab11和MYO5B相互作用，调节质膜蛋白的核内体运输，促进细胞运动。鼻咽癌（NPC）的内体运输系统尚不清楚。在这里，使用Oncomine数据库的离群分析表明Rab11- fip2在NPC中过表达，而Rab11和MYO5B则没有过表达。我们证实Rab11-FIP2的转录在鼻咽癌细胞系和原发肿瘤组织中与正常鼻咽上皮细胞系和正常鼻咽组织相比上调。我们进一步证实了Rab11-FIP2蛋白在NPC活检中的表达水平升高。敲低Rab11-FIP2并不调节上皮-间质转化或Akt信号通路，而是通过降低Rac和Cdc42的表达来抑制鼻咽癌细胞系的迁移和侵袭能力。综上所述，Rab11-FIP2可能是鼻咽癌的一个癌基因，主要通过激活Rho GTPase信号传导来促进转移能力。
Rab11 family interacting protein 2 (Rab11-FIP2) is a conserved protein and effector molecule for the small GTPase Rab11. By interacting with Rab11 and MYO5B, Rab11-FIP2 regulates endosome trafficking of plasma membrane proteins, promoting cellular motility. The endosomal trafficking system in nasopharyngeal carcinoma (NPC) remains unclear. Here, an outlier analysis using the Oncomine database suggested that Rab11-FIP2 but not Rab11 and MYO5B was overexpressed in NPC. We confirmed that the transcription of Rab11-FIP2 was upregulated in NPC cell lines and primary tumor tissues as compared with a normal nasopharyngeal epithelial cell line and normal nasopharynx tissues. We further confirmed the elevated protein expression level of Rab11-FIP2 in NPC biopsies. Instead of regulating the epithelial-mesenchymal transition or Akt signaling pathway, knockdown of Rab11-FIP2 inhibited the migration and invasion ability of NPC cell lines by decreasing the expression of Rac and Cdc42. In summary, Rab11-FIP2 could be an oncogene in NPC, mainly contributing to metastatic capacity by activating Rho GTPase signaling.