食管鳞癌转移机制不明，缺乏有效治疗靶点和药物。前期发现生长激素释放激素受体（GHRH-R）在食管鳞癌中高表达，且GHRH-R拮抗剂MIA-602抑制肿瘤细胞侵袭和糖酵解。生物信息分析和细胞实验发现糖酵解限速酶PFKM可能介导MIA-602对肿瘤细胞侵袭的抑制。进一步分析，发现NF-κB p65上调PFKM表达，而MIA-602下调p65表达，且过表达p65逆转MIA-602对PFKM的调节。假说：GHRH-R拮抗剂通过p65调节PFKM，进而调控肿瘤转移。本研究拟①应用细胞和小鼠模型，验证GHRH-R拮抗剂抑制肿瘤代谢和转移；②在体内外水平，验证PFKM介导GHRH-R拮抗剂调控肿瘤糖酵解和转移；③在分子水平探讨p65调节PFKM的机制，验证p65是介导GHRH-R拮抗剂调节PFKM表达的关键机制。本课题旨在探讨GHRH-R拮抗剂调控肿瘤糖代谢-转移的分子机制，为治疗转移提供新思路。

The molecular mechanism of metastasis in esophageal squamous cell carcinoma (ESCC) remains unclear, and there are no effective drugs owing to a lack of therapeutic targets. Our preliminary data showed that growth hormone-releasing hormone receptor (GHRH-R) was upregulated in ESCC, and GHRH-R antagonist MIA-602 inhibited glycolysis and invasion of ESCC cells. Bioinformatic analysis and in vitro studies indicated that the effect of MIA-602 on invasion was dependent on phosphofructokinase, muscle type (PFKM), a key glycolytic enzyme. Moreover, we showed that NF-κB p65 could increase the expression of PFKM. Further, MIA-602 was found to suppress the expression of p65. More importantly, overexpression of p65 reversed the inhibitory effect of MIA-602 on the expression of PFKM. We reasoned that MIA-602 represses ESCC metastasis through regulation of PFKM in a p65 dependent manner. We thus first set to clarify whether MIA-602 regulates metastasis via glycolysis, using cultured cells and mouse models. Second, we will verify that PFKM mediates MIA-602's effect on glycolysis and metastasis of cancer cells, using both in vitro and in vivo models. Third, we will elucidate that MIA-602 suppresses the expression of PFKM through downregulation of p65. The project aims to explore the regulatory mechanism, which GHRH-R antagonist uses to inhibit glycolysis-induced metastasis, and is favorable to design the novel therapeutic strategy against metastasis.