近年来研究认为，细胞融合可能是肿瘤侵袭和转移的基础，但目前对其分子机制和具体作用知之甚少。我们已发表的研究结果首次证实TNF-α能够促进口腔鳞癌-内皮细胞融合，本课题进一步提出"TNF-α通过Wnt/β-catenin通路激活途径上调syncytin以及α4β1表达，进而诱导口腔鳞癌-内皮细胞融合，后者可以促进肿瘤血管生成和转移"。本课题围绕上述研究假设，重点探讨①TNF-α对口腔鳞癌-内皮细胞融合的增效作用；②TNF-α对口腔鳞癌-内皮细胞融合过程中syncytin-1和α4β1表达的靶向调控作用；③Wnt/β-catenin信号通路激活在TNF-α促进口腔鳞癌-内皮细胞融合过程中的作用；④口腔鳞癌-内皮细胞融合在肿瘤血管生成中的潜在作用。研究结果将深入阐明TNF-α促进口腔鳞癌-内皮细胞融合的分子调控和信号转导机制，可能揭示细胞融合作为肿瘤血管生成的一种全新机制。

Recent studies postulate that cell fusion is one of the driving forces of cancer invasion and metastasis. However,the molecular mechanisms underlying cell fusion events and its detailed role in cancer biology are not well understood.Our recently published results are the first to confirm that TNF-α can enhance fusions between oral cancer cells and vascular endothelial cells. In this project,we hypothesize that TNF-α promote cancer-endothelial cell fusion through Wnt/β-catenin activation-mediated upregulation of fusogenic protein syncytin and α4β1, and that the cancer-endothelial cell fusion may also play potential roles in tumor angiogenesis.To confirm the above hypothesis, the present grant was designed to investigate ①the enhancing effect of TNF-αon oral cancer-endothelal cell fusion;②forward regulation of TNF-αon the expression of fusogenic protein syncytin-1and α4β1 during oral cancer-endothelial fusion；③role of Wnt/β-catenin signaling pathway activation in TNF-α-enhanced oral cancer-endothelial fusion；④potential roles of oral cancer-endothelial fusion in tumor angiogenesis and metastasis.Our results expect to provide insight into the molecular regulation and signal transduction mechanisms responsible for TNF-α-promoted oral cancer-endothelial cell fusion, and to clarify cell fusion as a novel potential mechanism underlying tumor angiogenesis.