RHAMM/hyaluronan inhibit β-catenin degradation, enhance downstream signaling, and facilitate fibrosarcoma cell growth.
Cell growth
Fibrosarcoma
Hyaluronan
Receptor for hyaluronic acid-mediated motility (RHAMM)
β-catenin
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
09
03
2023
accepted:
16
08
2023
medline:
10
11
2023
pubmed:
15
9
2023
entrez:
14
9
2023
Statut:
ppublish
Résumé
Increased hyaluronan deposition (HA) in various cancer tissues, including sarcomas, correlates with disease progression. The receptor for hyaluronic acid-mediated motility (RHAMM) expression is elevated in most human cancers. β-catenin is a critical downstream mediator of the Wnt signaling pathways, facilitating carcinogenic events characterized by deregulated cell proliferation. We previously showed that low molecular weight (LMW) HA/RHAMM/β-catenin signaling axis increases HT1080 fibrosarcoma cell growth. Here, focusing on mechanistic aspects and utilizing immunofluorescence and immunoprecipitation, we demonstrate that LMW HA treatment enhanced RHAMM intracellular localization (p ≤ 0.001) and RHAMM/β-catenin colocalization in HT1080 fibrosarcoma cells (p ≤ 0.05). Downregulating endogenous HA attenuated the association of RHAMM/β-catenin in HT1080 fibrosarcoma cells (p ≤ 0.0.01). Notably, Axin-2, the key β-catenin degradation complex component, and RHAMM were demonstrated to form a complex primarily to cell membranes, enhanced by LMW HA (p ≤ 0.01). In contrast, LMW HA attenuated the association of β-catenin and Axin-2 (p ≤ 0.05). The utilization of FH535, a Wnt signaling inhibitor, showed that LMW HA partially rescued the Wnt-dependent growth of HT1080 cells and restored the expression of Wnt/β-catenin mediators, cyclin-D1 and c-myc (p ≤ 0.05). B6FS fibrosarcoma cells with different HA metabolism do not respond to the LMW HA growth stimulus (p = NS). The present study identifies a novel LMW HA/RHAMM mechanism in a fibrosarcoma model. LMW HA regulates intracellular RHAMM expression, which acts as a scaffold protein binding β-catenin and Axin-2 at different cellular compartments to increase β-catenin expression, transcriptional activity, and fibrosarcoma growth.
Identifiants
pubmed: 37710072
doi: 10.1007/s11033-023-08763-0
pii: 10.1007/s11033-023-08763-0
doi:
Substances chimiques
Hyaluronic Acid
9004-61-9
Axin Protein
0
beta Catenin
0
Hyaluronan Receptors
0
Carrier Proteins
0
Extracellular Matrix Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8937-8947Subventions
Organisme : Special Account for Research Funds of University of Crete (SARF UoC)
ID : 10333
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
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