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CLEC18A interacts with sulfated GAGs and controls clear cell renal cell carcinoma progression
Open accessPreprint — published as 10.1111/febs.70236 · Paper page
Abstract
C-type lectins are a large family of proteins with essential functions in both health and disease. In cancer, some C-type lectins have been found to both promote and inhibit tumor growth, but many of the C-type lectins still remain uncharacterised in a tumor context. Therefore, there is growing interst in further elucidating the mechanisms with which C-type lectins control tumor growth. Here, we report a key role of the CLEC18 family of C-type lectins in the progression of clear cell renal cell carcinoma (ccRCC). The CLEC18 family is conserved across the entire Chordata phylum with recent gene duplication events in humans. We found that CLEC18A is exclusively expressed in the proximal tubule of the kidney and the medial habenula of the brain. We further identified sulfated glycosaminoglycans (GAGs) of proteoglycans as the main CLEC18A ligand, making them unique among C-type lectins. In ccRCC patients, high expression of the CLEC18 family lectins in the tumor are associated with improved survival. In mouse models of ccRCC, deletion of the mouse ortholog Clec18a resulted in enhanced tumor growth. Our results establishes CLEC18A as a novel and critical regulators of ccRCC tumor growth and highlights the potential benefit of modulating CLEC18 expression in the renal tumor microenvironment.
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Metadata
- Authors
- Jonsson, G., Hofmann, M., Mereiter, S., Hartley-Tassell, L., Sakic, I., Oliveira, T., Hoffmann, D., Novatchkova, M., Schleiffer, A., & Penninger, J. M.
- Affiliations
- Institute of Molecular Biotechnology (AT)
- Corresponding author
- Jonsson, Gustav
- Penninger, Josef M.
- ORCID
- Venue
- FEBS Journal
- Publisher
- openRxiv
- Published
- 2024-07-10
- Volume
- 293
- Issue
- 3
- Pages
- 709-728
- ISSN
- 1742-464X (ISSN-L)
- PMC
- PMC12871919
- OpenAlex
- W4413471203
- Cited by
- 1
- References
- 3
- Citations by year
- 2025: 1
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- FEBS Journal (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Fundació la Marató de TV3 (202125-31)
- European Commission (841319, HORIZON2020)
- Canada Research Chairs (F18‐01336)
- Österreichischen Akademie der Wissenschaften
- Bundesministerium für Bildung und Forschung (01KX2324)
- Austrian Science Fund (ESP 166)
- Universität Wien
- Medizinische Universität Wien
- T. Von Zastrow Foundation
- H2020 Marie Skłodowska-Curie Actions (841319)
- Topics
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
- Keywords
- C-type lectin, clear cell renal cell carcinoma, sulfated glycosaminoglycans, tumor progression, tumor microenvironment, proximal tubule, medial habenula, gene duplication, tumor growth, patient survival
- MeSH terms
- Animals, Carcinoma, Renal Cell, Glycosaminoglycans, Humans, Kidney Neoplasms, Gene Expression Regulation, Neoplastic, Disease Progression, Lectins, C-Type, Cell Line, Tumor, Mice
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