肿瘤血管生成拟态是一种独立于肿瘤血管内皮细胞出芽式生长的肿瘤功能性微循环模式，在肿瘤的发生、进展过程中发挥了重要作用。但是，触发血管生成拟态过程的驱动因子及其分子作用机制至今尚未被阐明，严重限制了研究者对于肿瘤发生过程的完整理解。申请人在前期研究基础上，结合对于血管生成拟态发生关键分子Endoglin的功能分析，提出“Endoglin蛋白 与PP2A分子的相互作用及对下游信号通路的激活是促进肿瘤血管生成拟态形成的驱动因素”这一新型机制假说。围绕这一假说，申请人计划在本实验中，以口腔鳞癌为疾病模型，聚焦研究Endoglin与PP2A蛋白相互作用对于肿瘤细胞转分化、细胞可塑性变化、细胞内外信号调节激酶活性、细胞外基质重构的影响，以证实其对于肿瘤血管生成拟态发生过程的驱动作用，初步揭示其调控机制与网络，并对于新型肿瘤血管生成拟态靶向干预手段在口腔鳞癌治疗中的应用开展体内外实验研究。

Vasculogenic mimicry is a kind of new pattern of tumor microcirculation, which is totally different from the classic tumor angiogenesis and independent of vascular endothelial cells. During tumor progress, vasculogenic mimicry plays an important role. However, the driving factors of vasculogenic mimicry remain elusive, which severely limits the understanding of carcinogenesis. Based on the preliminary study, combining the function analysis of Endoglin, one key molecule of vasculogenic mimicry, we proposed that “the interaction between Endoglin and PP2A and subsequent activation of downstream signaling events might trigger the formation of vasculogenic mimicry”. According to this hypothesis, in this study, we are going to investigate the function of Endoglin-PP2A interaction on tumor cell transdifferentiation, cell plasticity, the intra and extra cellular signal regulating kinase activity changes, and the effects of extracellular matrix remodeling, to uncover the driving factors of tumor vasculogenic mimicry and its regulation network. And the novel vasculogenic mimicry targeted treatment will also be evaluated in vivo and in vitro.