在恶性肿瘤的发展过程中，细胞外基质（ECM）通常受到异常调节。赖氨酰氧化酶样 2 (LOXL2)、基质金属蛋白酶 9 (MMP9) 和脂质运载蛋白 2 (LCN2) 的表达失调与 ECM 重塑相关。在本研究中，蛋白质-蛋白质相互作用测定表明LCN2和LOXL2相互作用以及LCN2和MMP9相互作用均发生在细胞内和细胞外，但LOXL2和MMP9之间的相互作用仅发生在细胞内。 LCN2/LOXL2/MMP9三元复合物促进食管鳞状细胞癌（ESCC）细胞的迁移和侵袭，以及体内肿瘤生长和恶性进展，而铁螯合剂甲磺酸去铁胺（DFOM）抑制食管鳞状细胞癌肿瘤生长。 LCN2、LOXL2和MMP9的共过表达增强了肿瘤细胞降解纤连蛋白和基质胶的能力，增加了丝状伪足的形成和延伸，并通过上调profilin 1促进微丝重排。此外，LCN2/LOXL2/MMP9三元复合物促进testican-1（SPOCK1）的表达，并异常激活FAK/AKT/GSK3β信号通路。综上所述，LCN2/LOXL2/MMP9三元复合物通过多种机制促进癌细胞的迁移和侵袭以及恶性肿瘤的进展，可能成为潜在的治疗靶点。© 2023 作者。约翰·威利出版的《分子肿瘤学》

During malignant tumour development, the extracellular matrix (ECM) is usually abnormally regulated. Dysregulated expression of lysyl oxidase-like 2 (LOXL2), matrix metalloproteinase 9 (MMP9) and lipocalin 2 (LCN2) are associated with ECM remodelling. In this study, protein-protein interaction assays indicated that LCN2 and LOXL2 interactions and LCN2 and MMP9 interactions occurred both intracellularly and extracellularly, but interactions between LOXL2 and MMP9 only occurred intracellularly. The LCN2/LOXL2/MMP9 ternary complex promoted migration and invasion of oesophageal squamous cell carcinoma (ESCC) cells, as well as tumour growth and malignant progression in vivo, while the iron chelator deferoxamine mesylate (DFOM) inhibited ESCC tumour growth. Co-overexpression of LCN2, LOXL2 and MMP9 enhanced the ability of tumour cells to degrade fibronectin and Matrigel, increased the formation and extension of filopodia, and promoted the rearrangement of microfilaments through upregulation of profilin 1. In addition, the LCN2/LOXL2/MMP9 ternary complex promoted the expression of testican-1 (SPOCK1), and abnormally activated the FAK/AKT/GSK3β signalling pathway. In summary, the LCN2/LOXL2/MMP9 ternary complex promoted the migration and invasion of cancer cells and malignant tumour progression through multiple mechanisms and could be a potential therapeutic target.© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.