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

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,...

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Autores principales:	Patrick Meylan, Christine Pich, Carine Winkler, Stefanie Ginster, Lionel Mury, Marie Sgandurra, René Dreos, Dennie Tompers Frederick, Marc Hammond, Genevieve Marie Boland, Liliane Michalik
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/afba53c8238a4f37922879d894340072
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spelling	oai:doaj.org-article:afba53c8238a4f37922879d8943400722021-12-02T15:51:14ZLow expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases10.1038/s41598-021-86329-52045-2322https://doaj.org/article/afba53c8238a4f37922879d8943400722021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86329-5https://doaj.org/toc/2045-2322Abstract 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.Patrick MeylanChristine PichCarine WinklerStefanie GinsterLionel MuryMarie SgandurraRené DreosDennie Tompers FrederickMarc HammondGenevieve Marie BolandLiliane MichalikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patrick Meylan Christine Pich Carine Winkler Stefanie Ginster Lionel Mury Marie Sgandurra René Dreos Dennie Tompers Frederick Marc Hammond Genevieve Marie Boland Liliane Michalik Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases
description	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.
format	article
author	Patrick Meylan Christine Pich Carine Winkler Stefanie Ginster Lionel Mury Marie Sgandurra René Dreos Dennie Tompers Frederick Marc Hammond Genevieve Marie Boland Liliane Michalik
author_facet	Patrick Meylan Christine Pich Carine Winkler Stefanie Ginster Lionel Mury Marie Sgandurra René Dreos Dennie Tompers Frederick Marc Hammond Genevieve Marie Boland Liliane Michalik
author_sort	Patrick Meylan
title	Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases
title_short	Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases
title_full	Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases
title_fullStr	Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases
title_full_unstemmed	Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases
title_sort	low expression of the pparγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/afba53c8238a4f37922879d894340072
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Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases

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