serval:BIB_E6198EE2A6D0
Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases.
10.1038/s41598-021-86329-5
000640426600005
33846376
Meylan
P.
author
Pich
C.
author
Winkler
C.
author
Ginster
S.
author
Mury
L.
author
Sgandurra
M.
author
Dreos
R.
author
Frederick
D.T.
author
Hammond
M.
author
Boland
G.M.
author
Michalik
L.
author
article
2021-04-12
Scientific reports
2045-2322
2045-2322
journal
11
1
7847
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.
eng
60_published
true
peer-reviewed
Publication types: Journal Article
Publication Status: epublish
University of Lausanne
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