最新研究认为：肿瘤细胞EMT/MET可塑性赋予肿瘤干细胞不同特性，参与肿瘤转移不同阶段，肿瘤缺氧和炎症微环境在这一过程中发挥关键作用。课题组前期研究发现：缺氧和炎症的共同节点蛋白- - 巨噬细胞移动抑制因子(MIF)，是缺氧诱导口腔鳞癌EMT转化的重要炎症因子。据此提出假设：MIF/CD74通路在缺氧和炎症微环境调控口腔鳞癌EMT/MET可塑性和干性中可能发挥重要作用。拟从肿瘤炎症和缺氧微环境整体角度，以MIF/CD74为切入点，以EMT/MET可塑性和干性为中轴线，探讨MIF/CD74通过哪些下游基因、蛋白和miRNAs及信号通路在转移不同阶段调控口腔鳞癌EMT或MET发生？决定哪些干性特征？其能量代谢重编程特点是什么？肿瘤微环境又在其中起何作用？结果将全面动态诠释口腔鳞癌炎症和缺氧微环境中MIF/CD74通路调控EMT/MET可塑性和干性促进转移的分子机制，为口腔鳞癌转移的防治提供新思路。

EMT is first acquired in the onset of transmigration in tumor metastasis and then reversed MET in the new colony, thus the all-encompassing has been termed EMT/MET plasticity. Recently, it has been reported that EMT/MET plasticity of cancer can endow different characteristics of cancer stem cells (CSC) in tumor metastatic cascade, and tumor-associated hypoxia and inflammation microenvironments may play a critical role in this process. Our previous data have shown that migration inhibitory factor (MIF), as a linking of hypoxia and inflammation, is one of important inflammation factors in hypoxia inducing EMT of oral squamous cell carcinoma (OSCC) detected by Cytokine Array. Yet, there are many uncharted territories in this field that we have to shed more light on. Thus, we hypotheses that tumor-associated hypoxia and inflammation microenvironments could mediate EMT/MET plasticity and stemness of OSCC through MIF/CD74 signaling pathway. In this project, we will investigate the molecular mechanisms of the following questions: 1) How do MIF/CD74 signaling pathway regulate EMT/MET plasticity and different stemness of OSCC; and how do EMT/MET plasticity endow different stemness of OSCC in this process? 2) To select the key genes, proteins, microRNAs and signaling pathways involved in the EMT/MET plasticity and different stemness mediated by MIF/CD74 pathway in tumor microenvironment; 3)In addition, what are the characteristics and significance of the energy programming in this process? The discoveries of this project in the tumor metastasis field will lead to better definition of MIF/CD74 signaling pathway affected by inflammation and hypoxia microenvironment and the molecular mechanisms by which it modifies metastatic niche formation. This should pave the way toward a better understanding of tumor-associated microenvironment contributing to EMT/MET plasticity and the origin of CSC, as well as novel therapeutics targets to eradicate subpopulation of therapy-refractory cancer cells with metastatic and stem cells capacities. They may even yield new therapeutic targets to the medication prevention of OSCC metastasis in the future.