胃癌（GC）是一种恶性肿瘤，具有很高的死亡率，肝转移是预后不良的主要原因之一。SLIT-和NTRK-like家族成员4（SLITRK4）在神经系统中具有重要作用，如突触形成。我们的研究旨在探讨SLITRK4在GC和肝转移中的功能作用。使用公开可用的转录组GEO数据集和Renji队列评估了SLITRK4的mRNA水平。使用免疫组化观察了GC组织微阵列中SLITRK4的蛋白质水平。进行细胞计数试剂盒-8、集落形成、体外转移实验和体内小鼠肝转移模型，以研究SLITRK4在GC中的功能角色。应用生物信息学预测和Co-IP实验进行SLITRK4结合蛋白的筛选和鉴定。进行Western blot以检测酪氨酸激酶受体B（TrkB）相关信号分子。通过比较GC的原发灶和肝转移灶，发现SLITRK4在具有肝转移的GC组织中上调，并与不良临床预后密切相关。SLITRK4敲除显著抑制了GC在体内和体外的生长、侵袭和转移。进一步研究表明，SLITRK4可以与Canopy FGF信号调节因子3（CNPY3）相互作用，从而通过促进TrkB受体的内吞和回收而增强TrkB相关信号。总之，CNPY3-SLITRK4轴通过TrkB相关信号通路促进了GC的肝转移，可能是治疗具有肝转移的GC的治疗靶点。©2023.Springer Nature Switzerland AG.

Gastric cancer (GC) is a malignant tumour with high mortality, and liver metastasis is one of the main causes of poor prognosis. SLIT- and NTRK-like family member 4 (SLITRK4) plays an important role in the nervous system, such as synapse formation. Our study aimed to explore the functional role of SLITRK4 in GC and liver metastasis.The mRNA level of SLITRK4 was evaluated using publicly available transcriptome GEO datasets and Renji cohort. The protein level of SLITRK4 in the tissue microarray of GC was observed using immunohistochemistry. Cell Counting Kit-8, colony formation, transwell migration assays in vitro and mouse model of liver metastasis in vivo was performed to investigate the functional roles of SLITRK4 in GC. Bioinformatics predictions and Co-IP experiments were applied to screen and identify SLITRK4-binding proteins. Western blot was performed to detect Tyrosine Kinase receptor B (TrkB)-related signaling molecules.By comparing primary and liver metastases from GC, SLITRK4 was found to be upregulated in tissues of GC with liver metastasis and to be closely related to poor clinical prognosis. SLITRK4 knockdown significantly abrogated the growth, invasion, and metastasis of GC in vitro and in vivo. Further study revealed that SLITRK4 could interact with Canopy FGF Signalling Regulator 3 (CNPY3), thus enhancing TrkB- related signaling by promoting the endocytosis and recycling of the TrkB receptor.In conclusion, the CNPY3-SLITRK4 axis contributes to liver metastasis of GC according to the TrkB-related signaling pathway. which may be a therapeutic target for the treatment of GC with liver metastasis.© 2023. Springer Nature Switzerland AG.