Upregulation of flotillin-1 promotes invasion and metastasis by activating TGF-β signaling in nasopharyngeal carcinoma
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Sumei Cao1,2,*, Yanmei Cui1,*, Huiming Xiao3,*, Miaoqing Mai4, Chanjuan Wang5, Shanghang Xie2, Jing Yang6, Shu Wu1, Jun Li7, Libing Song1, Xiang Guo1,6, Chuyong Lin1
1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
2Department of Cancer Prevention Research, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China
3Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
4Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China
5Department of the Central Laboratory, The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, China
6Department of Nasopharyngeal Carcinoma, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China
7Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
*These author contributed equally to this work
Chuyong Lin, e-mail: Linc[email protected]
Xiang Guo, e-mail: [email protected]
Keywords: nasopharyngeal carcinoma, lymph node metastasis, flotillin-1, TGF-β signaling
Received: July 07, 2015 Accepted: November 25, 2015 Published: December 07, 2015
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.
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