Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases.

Details

Ressource 1Download: 2021_Meylan_SciReports.pdf (2407.39 [Ko])
State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_E6198EE2A6D0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases.
Journal
Scientific reports
Author(s)
Meylan P., Pich C., Winkler C., Ginster S., Mury L., Sgandurra M., Dreos R., Frederick D.T., Hammond M., Boland G.M., Michalik L.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
12/04/2021
Peer-reviewed
Oui
Volume
11
Number
1
Pages
7847
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
04/05/2021 7:32
Last modification date
22/05/2021 5:34
Usage data