Up-regulation of syncytin-1 contributes to TNF-α-enhanced fusion between OSCC and HUVECs partly via Wnt/β-catenin-dependent pathway.
Up-regulation of syncytin-1 contributes to TNF-α-enhanced fusion between OSCC and HUVECs partly via Wnt/β-catenin-dependent pathway.
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Syncytin-1 的上调部分通过 Wnt/β-catenin 依赖性途径促进 TNF-α 增强 OSCC 和 HUVEC 之间的融合
DOI：
10.1038/srep40983
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发表时间：
2017-01-23
影响因子：
4.6
通讯作者：
Shang ZJ
中科院分区：
文献类型：
--
作者：
Yan TL;Wang M;Xu Z;Huang CM;Zhou XC;Jiang EH;Zhao XP;Song Y;Song K;Shao Z;Liu K;Shang ZJ
越来越多的证据表明，细胞融合是肿瘤侵袭和转移的驱动力之一。然而，对于与癌症-宿主细胞融合相关的触发因素和潜在机制，特别是在炎症性肿瘤微环境中，所知甚少。在本研究中，我们证实炎症因子TNF-α可以促进鳞状细胞癌细胞9 （SCC-9）与人脐静脉内皮细胞（HUVEC）的融合。进一步研究发现TNF-α可促进HUVEC SCC-9及其受体中性氨基酸转运蛋白2 （ASCT-2）中syncytin-1的上调。Syncytin-1在TNF-α-增强的癌内皮细胞融合中发挥重要的下游效应。TNF-α处理也导致SCC-9中Wnt/β-catenin信号通路的激活。Wnt/β-catenin信号通路的激活与SCC-9中syncytin-1的上调和SCC-9与HUVEC融合增加密切相关，而Wnt/β-catenin信号通路的阻断导致syncytin-1的相应下调，并伴有癌内皮细胞融合的急剧下降。综上所述，我们的研究结果表明，Wnt/β-catenin信号通路激活依赖性的syncytin-1上调参与了促炎因子TNF-α-在口腔鳞状细胞癌细胞与内皮细胞之间的融合。
Accumulating evidence implies that cell fusion is one of the driving forces of cancer invasion and metastasis. However, considerably less is still known about the triggering factors and underlying mechanisms associated with cancer-host cell fusion, particularly in inflammatory tumor microenvironment. In this study, we confirmed that inflammatory factor TNF-α could enhance fusion between squamous cell carcinoma cells 9 (SCC-9) and human umbilical vein endothelial cells (HUVEC). Further study revealed that TNF-α could promote up-regulation of syncytin-1 in SCC-9 and its receptor neutral amino acid transporter type 2 (ASCT-2) in HUVEC. Syncytin-1 acted as an important downstream effector in TNF-α-enhanced cancer-endothelial cell fusion. TNF-α treatment also led to the activation of Wnt/β-catenin signal pathway in SCC-9. The activation of Wnt/β-catenin signal pathway was closely associated with the up-regulation of syncytin-1 in SCC-9 and increased fusion between SCC-9 and HUVEC while blocking of Wnt/β-catenin signal pathway resulted in the corresponding down-regulation of syncytin-1 accompanied by sharp decrease of cancer-endothelial cell fusion. Taking together, our results suggest that Wnt/β-catenin signal pathway activation-dependent up-regulation of syncytin-1 contributes to the pro-inflammatory factor TNF-α-enhanced fusion between oral squamous cell carcinoma cells and endothelial cells.