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Upregulation of flotillin-1 promotes invasion and metastasis by activating TGF-β signaling in nasopharyngeal carcinoma

2015; Impact Journals LLC; Volume: 7; Issue: 4 Linguagem: Inglês

10.18632/oncotarget.6483

1949-2553

Su‐Mei Cao, Yanmei Cui, Huiming Xiao, Miaoqing Mai, Chanjuan Wang, Shang-Hang Xie, Jing Yang, Shu Wu, Jun Li, Libing Song, Xiang Guo, Chuyong Lin,

Kruppel-like factors research

// Sumei Cao 1, 2, * , Yanmei Cui 1, * , Huiming Xiao 3, * , Miaoqing Mai 4 , Chanjuan Wang 5 , Shanghang Xie 2 , Jing Yang 6 , Shu Wu 1 , Jun Li 7 , Libing Song 1 , Xiang Guo 1, 6 , Chuyong Lin 1 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 2 Department of Cancer Prevention Research, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China 3 Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510080, China 4 Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China 5 Department of the Central Laboratory, The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, China 6 Department of Nasopharyngeal Carcinoma, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China 7 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China * These author contributed equally to this work Correspondence to: Chuyong Lin, e-mail: Linchuyong999@gmail.com Xiang Guo, e-mail: Guoxiang@sysucc.org.cn Keywords: nasopharyngeal carcinoma, lymph node metastasis, flotillin-1, TGF-β signaling Received: July 07, 2015 Accepted: November 25, 2015 Published: December 07, 2015 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.