title: Flotillin-2 promotes nasopharyngeal carcinoma metastasis and is necessary for the epithelial-mesenchymal transition induced by transforming growth factor-β.
abstract: Transforming growth factor-β (TGF-β) promotes cancer metastasis via the epithelial-mesenchymal transition (EMT) but the underlying mechanisms in nasopharyngeal carcinoma (NPC) remain unclear. Flotillin-2 (Flot2), a specialized lipid raft domain in cellular membrane, was reported to promote cancer metastasis. Recently, in neuropathy, it was also suggested that Flot2 was involved in Src activation, which is known as the downstream signal of TGF-β. Therefore, we intended to find out the relationship between Flot2 and TGF-β in the process of nasopharyngeal carcinoma (NPC) metastasis. In this study, we found that Flot2 expression level positively correlated with the cancer stage in NPC tissues. Elevated Flot2 in tumor tissue was an independent prognostic marker, and higher Flot2 expression level showed shorter overall survival time in 181 NPC patients. In NPC cells, silencing Flot2 reversed the metastatic effect induced by TGF-β. Moreover, TGF-β-induced Src phosphorylation was significantly inhibited by Flot2 knocking down. As the consequence of Flot2 inhibition, the expression of the epithelial biomarker E-cadherin was upregulated, while the mesenchymal marker vimentin and signaling transducer β-catenin was suppressed. In conclusions, Flot2 is an indispensable member for TGF-β signaling, which is essential for the EMT process in NPC metastasis. Suppressing Flot2 may be a novel way against TGF-β-induced EMT.
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.
authors.forename: Changqie
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Liao
mesh_terms: D000368:Aged; D015703:Antigens, CD; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D021962:Membrane Microdomains; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014945:Wound Healing
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C513384:CDH1 protein, human; D015820:Cadherins; D008565:Membrane Proteins; D053773:Transforming Growth Factor beta1; C106354:flotillins
keywords: Flotillin-2; epithelial-mesenchymal transition; metastasis; nasopharyngeal carcinoma; transforming growth factor-β