肿瘤转移是非小细胞肺癌(NSCLC)高致死率的主要原因，寻找关键调控基因，阐明其在转移中的功能及分子机制，对NSCLC转移患者的诊断治疗具有重要意义。前期通过PDCX转移模型，筛选出GOLPH3在NSCLC高转移组织中显著上调。体内外实验发现：①GOLPH3促进外泌体分泌，增强肿瘤干细胞特性，血管生成及EMT现象，多层面促进NSCLC转移；②GOLPH3与CKAP4互作，促进外泌体源性WNT3A分泌，激活Wnt/β-catenin信号通路，增强NSCLC的转移。进一步将①探索GOLPH3与CKAP4互作的具体区段，及调控外泌体源性WNT3A分泌的分子机制；②通过NSCLC患者组织及血液样本，探讨GOLPH3及其调控基因的表达与NSCLC预后及转移的临床相关性。本项目将揭示GOLPH3多层面调控NSCLC转移的分子机制，为GOLPH3作为NSCLC预后，转移及诊断治疗的潜在靶点提供科学依据。

Tumor metastasis is the main cause of high lethality in non-small cell lung cancer (NSCLC). Identifying key regulatory genes and clarifying its function and molecular mechanism in metastasis would be of great significance for the diagnosis and therapy of NSCLC patients with metastasis. Recently, using the RNA sequencing method, we found that GOLPH3 is one of the most significantly upregulated in the patient-derived cell xenograft (PDCX) metastasis model. Furthermore, we found that GOLPH3 can promote the secretion of exosome and enhance tumor stem cell-like phenotype, angiogenesis and EMT to promote NSCLC metastasis. We then demonstrated GOLPH3 interacted with CKAP4 can promote the secretion of exosomal WNT3A and enhance the activity of Wnt / β-catenin signaling pathways. Moreover, we will explore the specific interaction domain between GOLPH3 and CKAP4, and the molecular mechanism of regulating the secretion of exosomal WNT3A. We also use immunohistochemistry, western blot and ELISA assays to exploring the relationship between the expression of GOLPH3 and its regulatory genes in NSCLC tissues and blood samples. This project will reveal the molecular mechanism of GOLPH3 enhances NSCLC metastasis via the secretion of exsome and the activity of Wnt / β-catenin signaling pathways, which might provide new biomarkers and targets for the diagnosis and treatment of NSCLC.