淋巴转移是子宫内膜癌主要转移途径，淋巴管生成是促成肿瘤淋巴转移的核心事件，但其调控机制不清。新近研究表明，肿瘤微环境中间质细胞可通过外泌体途径调控肿瘤进展，我们前期RNA-seq分析发现，子宫内膜癌间质细胞源外泌体中下调最显著的miR-136可影响癌上皮细胞代谢及体外脉管形成，并能调控与代谢及转移密切相关的雌激素相关受体γ（ERRγ）蛋白的表达，阻断糖酵解可逆转miR-136下调诱导的体外脉管形成。由此，我们提出假设：子宫内膜癌间质细胞向上皮细胞递送的外泌体miR-136水平下降，通过上调ERRγ诱导子宫内膜癌细胞代谢重编程，促进子宫内膜癌淋巴管的生成及转移。本研究将在前期研究基础上，从细胞分子-动物-临床组织三个层面，结合多种动物模型，阐明miR-136/ERRγ介导癌间质细胞调控上皮细胞代谢促子宫内膜癌淋巴转移的内在机制，为子宫内膜癌淋巴转移的防治提供新思路。

Lymphatic metastasis is the major diffusion route in endometrial cancer (EC), and lymphangiogenesis is an important factor contributing to tumor lymphatic metastasis with undefined regulatory mechanism. Recent studies have shown that mesenchymal cells can participate in the regulation of tumor progression. Our previous studies have found that there are many differentially expressed miRNAs in exosomes from EC mesenchymal cells. miR-136 was the most down-regulated miRNA which involved in cell metabolism and ERRγ expression regulation, while ERRγ have been shown to participate in EC metastasis, and blocking glycolysis can reverse microRNA-136-induced angiogenesis in vitro. Accordingly, we hypothesize that the decrease of miRNA-136 in mesenchymal cell exosomes can lead to epithelial cell metabolic reprogramming via ERRγ，which further promoting endometrial cancer lymphatic metastasis. This project is proposed to clarify the intrinsic regulatory mechanism of cancer stromal cells affecting lymphatic metastasis of EC through cancer cell metabolism regulation from cell, molecular, animal and clinical levels, and attempt to provide novel approach for EC lymphatic metastasis prevention and treatment.