Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
J Cell Biochem. 2020 Feb;121(2):1072-1086. doi: 10.1002/jcb.29344. Epub 2019 Aug 26.
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.
Rab11 家族相互作用蛋白 2(Rab11-FIP2)是一种保守的蛋白质,也是小 GTPase Rab11 的效应分子。通过与 Rab11 和 MYO5B 相互作用,Rab11-FIP2 调节质膜蛋白的内体运输,促进细胞运动。鼻咽癌(NPC)中的内体运输系统仍不清楚。在这里,使用 Oncomine 数据库进行异常值分析表明,Rab11-FIP2 而不是 Rab11 和 MYO5B 在 NPC 中过表达。我们证实与正常鼻咽上皮细胞系和正常鼻咽组织相比,Rab11-FIP2 的转录在 NPC 细胞系和原发性肿瘤组织中上调。我们进一步证实了 NPC 活检中 Rab11-FIP2 蛋白表达水平升高。Rab11-FIP2 的敲低通过降低 Rac 和 Cdc42 的表达抑制 NPC 细胞系的迁移和侵袭能力,而不是调节上皮-间充质转化或 Akt 信号通路。总之,Rab11-FIP2 可能是 NPC 中的一种癌基因,主要通过激活 Rho GTPase 信号来促进转移能力。