Ladinin-1（LAD1）是一种锚定丝蛋白，与多种癌症类型有关，包括结肠癌、肺癌和乳腺癌。然而，LAD1如何和为何引发胃癌（GC）仍不清楚。本研究进行了多次体外和体内功能增益和丧失实验，以确认LAD1的功能。采用质谱法寻找与LAD1相互作用的蛋白质。免疫沉淀分析揭示了LAD1促进恶性程度的机制。结果显示，LAD1在GC组织中过表达，LAD1表达增加的参与者显示较差的无病生存（DFS）和总体生存（OS）。在体和体外的皮下病人来源和细胞来源异种移植（PDX和CDX）肿瘤模型中，LAD1在促进细胞浸润、迁移、增殖和化疗抗性方面发挥作用。机制上，LAD1与波形蛋白（Vimentin）竞争性结合，阻止其与E3泛素连接酶巨细胞红斑连接蛋白（MAEA）相互作用，导致Vimentin K48链化泛素化减少，Vimentin蛋白水平在GC细胞中增加。总之，本研究提示由于能够抑制Vimentin-MAEA相互作用，LAD1被预测为GC的潜在预后生物标志物和治疗靶点。 © 2023. BioMed Central Ltd., part of Springer Nature.

Ladinin-1 (LAD1), an anchoring filament protein, has been associated with several cancer types, including cancers of the colon, lungs, and breast. However, it is still unclear how and why LAD1 causes gastric cancer (GC).Multiple in vitro and in vivo, functional gains and loss experiments were carried out in the current study to confirm the function of LAD1. Mass spectrometry was used to find the proteins that interact with LAD1. Immunoprecipitation analyses revealed the mechanism of LAD1 involved in promoting aggressiveness.The results revealed that the LAD1 was overexpressed in GC tissues, and participants with increased LAD1 expression exhibited poorer disease-free survival (DFS) and overall survival (OS). Functionally, LAD1 promotes cellular invasion, migration, proliferation, and chemoresistance in vivo and in vitro in the subcutaneous patient-and cell-derived xenograft (PDX and CDX) tumor models. Mechanistically, LAD1 competitively bound to Vimentin, preventing it from interacting with the E3 ubiquitin ligase macrophage erythroblast attacher (MAEA), which led to a reduction in K48-linked ubiquitination of Vimentin and an increase in Vimentin protein levels in GC cells.In conclusion, the current investigation indicated that LAD1 has been predicted as a possible prognostic biomarker and therapeutic target for GC due to its ability to suppress Vimentin-MAEA interaction.© 2023. BioMed Central Ltd., part of Springer Nature.