Titre
Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Meylan, P.
Auteure/Auteur
Pich, C.
Auteure/Auteur
Winkler, C.
Auteure/Auteur
Ginster, S.
Auteure/Auteur
Mury, L.
Auteure/Auteur
Sgandurra, M.
Auteure/Auteur
Dreos, R.
Auteure/Auteur
Frederick, D.T.
Auteure/Auteur
Hammond, M.
Auteure/Auteur
Boland, G.M.
Auteure/Auteur
Michalik, L.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2045-2322
Statut éditorial
Publié
Date de publication
2021-04-12
Volume
11
Numéro
1
Première page
7847
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
The thioredoxin system plays key roles in regulating cancer cell malignancy. Here we identify the Thioredoxin-interacting protein (TXNIP) as a gene, which expression is regulated by PPARγ in melanoma cells. We show that high TXNIP expression levels associate with benign melanocytic lesions, with tumor regression in patients on MAP kinase targeted therapy, with decreased proliferation in patients' melanoma biopsies, and with cell cycle arrest in human melanoma cell lines. In contrast, reduced TXNIP expression associates with advanced melanoma and with disease progression in patients. TXNIP depletion in human melanoma cells altered the expression of integrin beta-3 and the localization of the integrin alpha-v/beta-3 dimer at their surface. Moreover, TXNIP depletion affected human melanoma cell motility and improved their capacity to colonize mouse lungs in an in vivo assay. This study establishes TXNIP as a PPARγ-regulated gene in melanoma cells, thereby suggesting a link between these two proteins both involved in the regulation of cancer and of energy metabolism. It also reveals that the decrease in TXNIP expression, which is observed in advanced patient tumors, likely favors lung metastatic seeding of malignant cells.
PID Serval
serval:BIB_E6198EE2A6D0
PMID
Open Access
Oui
Date de création
2021-05-04T06:32:26.781Z
Date de création dans IRIS
2025-05-21T06:00:25Z
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Nom
2021_Meylan_SciReports.pdf
Version du manuscrit
published
Taille
2.35 MB
Format
Adobe PDF
PID Serval
serval:BIB_E6198EE2A6D0.P001
URN
urn:nbn:ch:serval-BIB_E6198EE2A6D00
Somme de contrôle
(MD5):fff593586c9c7cfeadc289de99358596