Upregulation of flotillin-1 promotes invasion and metastasis by activating TGF-β signaling in nasopharyngeal carcinoma.
Upregulation of flotillin-1 promotes invasion and metastasis by activating TGF-β signaling in nasopharyngeal carcinoma.
复制标题
鼻咽癌中 flotillin-1 的上调通过激活 TGF-β 信号传导促进侵袭和转移。
DOI：
10.18632/oncotarget.6483
复制
发表时间：
2016-01-26
期刊：
影响因子：
--
通讯作者：
Lin C
中科院分区：
文献类型：
--
作者：
Cao S;Cui Y;Xiao H;Mai M;Wang C;Xie S;Yang J;Wu S;Li J;Song L;Guo X;Lin C
转移是癌症相关死亡的主要原因。鼻咽癌具有局部侵袭严重、区域淋巴结转移发生率高的特点，预后较差。然而，诱导鼻咽癌淋巴结转移的潜在机制在很大程度上仍然未知。在此，我们报道了脂质筏的一个组成部分flotilin -1 (FLOT1)，它被报道参与肿瘤的进展，在有淋巴结转移的鼻咽癌样本中被强烈上调。在169个存档的临床NPC样本中，高FLOT1表达与N分类以及较差的总生存率和无病生存率显著相关。在体外，过表达FLOT1增强了鼻咽癌细胞的迁移和侵袭能力，更重要的是，在体内促进了鼻咽癌细胞向周围组织的侵袭和向淋巴结的转移。而鼻咽癌细胞中内源性FLOT1的沉默减少了局部淋巴结的侵袭和转移。此外，FLOT1诱导TGF-β1的表达和分泌，促进TGF-β/Smad3信号的激活，实现上皮-间质转化。我们的研究结果提供了新的证据，证明FLOT1在促进鼻咽癌侵袭行为中发挥重要作用，并为TGF-β信号的调控机制提供了新的见解。
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.