title: Upregulation of flotillin-1 promotes invasion and metastasis by activating TGF-β signaling in nasopharyngeal carcinoma.
abstract: Metastasis is the main cause of cancer-related deaths. Nasopharyngeal carcinoma (NPC) is characterized by severe local invasion and high incidence of regional lymph node metastasis, which represents poor prognosis. However, the underlying mechanism that induces lymph node metastasis of NPC remains largely unknown. Herein, we report that flotillin-1 (FLOT1), a component of lipid raft, which was reported to be involved in tumor progression, was robustly upregulated in the NPC samples with lymph node metastasis. High FLOT1 expression was significantly associated with N classification as well as poorer overall and disease-free survivals in 169 archived clinical NPC samples. Overexpression of FLOT1 enhanced the migratory and invasive abilities of NPC cells in vitro, and more importantly, promoted invasion into the surrounding tissues and metastasis to lymph nodes in vivo. Whereas silencing of endogenous FLOT1 in NPC cells decreased the local invasion and metastasis to lymph nodes. Furthermore, FLOT1 induced the expression and secretion of TGF-β1, facilitated the activation of TGF-β/Smad3 signaling to effectuate epithelial-mesenchymal transition. Our findings present new evidence that FLOT1 plays an important role in promoting aggressive behavior of NPC and provide new insights into the regulatory mechanism of TGF-β signaling.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Cancer Prevention Research, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Cao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
authors.forename: Miaoqing
authors.initials: M
authors.lastname: Mai
authors.affiliation: Department of the Central Laboratory, The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cancer Prevention Research, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
authors.forename: Shanghang
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Nasopharyngeal Carcinoma, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Nasopharyngeal Carcinoma, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Chuyong
authors.initials: C
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002277:Carcinoma; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D008565:Membrane Proteins; D016212:Transforming Growth Factor beta; C106354:flotillins
keywords: TGF-β signaling; flotillin-1; lymph node metastasis; nasopharyngeal carcinoma