title: Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-κB and PI3K/Akt3 signaling pathways.
abstract: Lipid raft proteins have been confirmed to be important in cell signal transduction. Some reports have shown that the aberrant expression of lipid raft proteins is associated with malignant phenotypes in some cancers. However, the role of the lipid raft protein flotillin-2 (Flot-2) in nasopharyngeal carcinoma (NPC) remains to be comprehensively characterized. Here, overexpression of Flot-2 in NPC tissues and cell lines was detected by immunostaining, and Flot-2 expression was found to be positively associated with NPC metastasis. Furthermore, inhibiting Flot-2 expression impaired the malignancy of the highly metastatic NPC cell line 5-8F by constraining its growth and proliferation, mobility and migration, and decreasing the capacity of 5-8F cells to metastasize in nude mice. In contrast, forced overexpression of Flot-2 increased the malignancy of 6-10B, a non-metastatic NPC cell line that weakly expresses Flot-2. Moreover, in 5-8F-shFlot-2 cells, which have inhibited Flot-2 expression, the NF-κB and PI3K/Akt3 pathways were inactivated. Subsequently, MMPs expression were decreased, and Foxo1 activity was increased. In addition, enhanced NF-κB and PI3K/Akt3 activities were observed in Flot-2 overexpressing 6-10B cells. Thus, Flot-2 exerts a pro-neoplastic role in NPC and is involved in tumor progression and metastasis. Moreover, Flot-2 exerts its role through NF-κB and PI3K/Akt3 signaling.
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Caiping
authors.initials: C
authors.lastname: Ren
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Qiuyuan
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Hunan Cancer Hospital, Changsha, Hunan, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Feng
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Xia
authors.affiliation: Hepatobiliary &Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D016328:NF-kappa B; C106354:flotillins; D019869:Phosphatidylinositol 3-Kinases; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt