NUMA1靶向调控GSTP1促进食管癌发生发展的机制研究

食管癌是一种常见的恶性肿瘤，是我国的第四大常见癌症。目前，由于缺乏有效的治疗靶点，食管癌的治疗效果并不理想。我们的前期研究结果发现：NUMA1在人食管癌细胞和组织中均高表达，并且与食管癌患者生存期呈负相关；降低NUMA1表达能够显著抑制食管癌细胞的增殖及克隆形成能力，促进细胞凋亡并将细胞周期阻滞在G1期；食管癌CDX和PDX模型研究发现，下调NUMA1表达能够显著抑制食管癌的生长；免疫共沉淀结果显示GSTP1可能是NUMA1的下游靶蛋白，NUMA1能够通过与GSTP1相互作用影响其调节的下游JNK信号通路的激活，提示NUMA1可能通过靶向调控GSTP1在食管癌的发生发展过程中发挥了重要功能。本项目拟通过免疫共沉淀，shRNA技术和基因条件敲除鼠等进一步研究NUMA1靶向调控GSTP1促进食管癌发生发展的作用机制，并通过体内外实验进行验证，为以NUMA1为靶点的食管癌治疗提供新的实验依据。

Esophageal cancer is one kind of common malignant, it is the fourth common cancer in China. Due to the lack of effective therapeutic targets, therapeutic effect of esophageal cancer is not ideal. Our previous study found that NUMA1 was highly expressed in human esophageal cancer cells and tissues, and its expression is negatively correlated with the survival time of patients; reducing NUMA1 expression could effectively inhibit cell proliferation and colony formation, promote cell apoptosis and block the cell cycle in G1 phase; In cell-derived xenograft model（CDX）and patient-derived xenograft model（PDX）, knock down NUMA1 expression could significantly inhibit tumor growth; The results of immunoprecipitation showed that GSTP1 may be the downstream target protein of NUMA1, and NUMA1 can affect the activation of the GSTP1 regulated downstream JNK signaling pathway by interacting with GSTP1, suggesting that NUMA1 may be played an important role in the occurrence and development of esophageal cancer by targeting and regulating GSTP1. This project intends to further study the mechanism of NUMA1 targeting and regulating GSTP1 to promote the occurrence and development of esophageal cancer through immunoprecipitation, shRNA technology and gene conditional knockout mice, verify the mechanism through in vivo and in vitro experiments, and provide new experimental basis for the prevention and treatment of esophageal cancer in the clinic.