2024/07/08 by Shengnan Yuan, Rachele Bacchetti, Jamie Adams +1 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Peptidase Inhibition and Analysis #Biochemical and Structural Characterization #Blood Coagulation and Thrombosis Mechanisms
paper · doi:10.1101/2024.07.08.602517
openalex publication_date 2024/07/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
Abstract Ovarian cancer is the 3 rd most common gynaecological malignancy worldwide, with a 5-year survival rate of less than 30% in the presence of metastasis. Metastatic progression is characterised by extensive remodelling of the extracellular matrix, primarily mediated by secreted matrix metalloproteinases, including members of the ‘a disintegrin and metalloprotease with thrombospondin motif’ (ADAMTS) family. In particular, ADAMTS5 has been reported to be upregulated in ovarian malignant tumours compared to borderline and benign lesions, suggesting it might play a role in metastatic progression. Furthermore, it has been suggested that Rab25, a small GTPase of the Ras family, might upregulate ADAMTS5 expression in ovarian cancer cells. Here we demonstrated that Rab25 promotes ADAMTS5 expression, through the activation of the NF-κB signalling pathway. Furthermore, ADAMTS5 was necessary and sufficient to stimulate ovarian cancer cell migration through complex fibroblast-secreted matrices, while ADAMTS5 inhibition prevented ovarian cancer spheroid invasion in 3D systems. Finally, in ovarian cancer patients high ADAMTS5 expression correlated with poor prognosis. Altogether, these data identify ADAMTS5 as a novel regulator of ovarian cancer cell migration and invasion, suggesting it might represent a novel therapeutic target to prevent ovarian metastasis.