The protease ADAMTS5 controls ovarian cancer cell invasion, downstream of Rab25
Author(s)
Type
Journal Article
Abstract
Ovarian cancer is the 3rd most common gynaecological malignancy worldwide, with a 5-year survival rate of < 30% in the presence of metastasis. Metastatic progression is characterised by extensive remodelling of the extracellular matrix, primarily mediated by secreted proteases, 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 nuclear factor κB (NF-κB) signalling pathway. Furthermore, ADAMTS5 was necessary and sufficient to stimulate ovarian cancer cell migration through complex fibroblast-secreted matrices, while selective 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 previously undescribed therapeutic target to prevent ovarian cancer metastasis.
Date Issued
2025-09-01
Date Acceptance
2025-03-20
Citation
The FEBS Journal, 2025, 292 (17), pp.4491-4515
ISSN
1742-464X
Publisher
Wiley
Start Page
4491
End Page
4515
Journal / Book Title
The FEBS Journal
Volume
292
Issue
17
Copyright Statement
© 2025 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40164572
Subjects
ADAMTS5
ECM
Rab25
cancer cell invasion
ovarian cancer
Humans
Female
Ovarian Neoplasms
ADAMTS5 Protein
Cell Movement
Neoplasm Invasiveness
Cell Line, Tumor
rab GTP-Binding Proteins
Gene Expression Regulation, Neoplastic
Signal Transduction
NF-kappa B
Prognosis
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-03-31