Ciglitazone negatively regulates CXCL1 signaling through MITF to suppress melanoma growth.

Détails

ID Serval
serval:BIB_8E9D6C762ECB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Ciglitazone negatively regulates CXCL1 signaling through MITF to suppress melanoma growth.
Périodique
Cell Death and Differentiation
Auteur(s)
Botton T., Puissant A., Cheli Y., Tomic T., Giuliano S., Fajas L., Deckert M., Ortonne J.P., Bertolotto C., Tartare-Deckert S., Ballotti R., Rocchi S.
ISSN
1476-5403 (Electronic)
ISSN-L
1350-9047
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
18
Numéro
1
Pages
109-121
Langue
anglais
Résumé
We have previously demonstrated that the thiazolidinedione ciglitazone inhibited, independently of PPARγ activation, melanoma cell growth. Further investigations now show that ciglitazone effects are mediated through the regulation of secreted factors. Q-PCR screening of several genes involved in melanoma biology reveals that ciglitazone inhibits expression of the CXCL1 chemokine gene. CXCL1 is overexpressed in melanoma and contributes to tumorigenicity. We show that ciglitazone induces a diminution of CXCL1 level in different human melanoma cell lines. This effect is mediated by the downregulation of microphthalmia-associated transcription factor, MITF, the master gene in melanocyte differentiation and involved in melanoma development. Further, recombinant CXCL1 protein is sufficient to abrogate thiazolidinedione effects such as apoptosis induction, whereas extinction of the CXCL1 pathway mimics phenotypic changes observed in response to ciglitazone. Finally, inhibition of human melanoma tumor development in nude mice treated with ciglitazone is associated with a strong decrease in MITF and CXCL1 levels. Our results show that anti-melanoma effects of thiazolidinediones involve an inhibition of the MITF/CXCL1 axis and highlight the key role of this specific pathway in melanoma malignancy.
Mots-clé
Animals, Antineoplastic Agents/therapeutic use, Apoptosis, Cell Differentiation, Cell Line, Tumor, Chemokine CXCL1/genetics, Chemokine CXCL1/metabolism, Down-Regulation, Humans, Melanoma/drug therapy, Melanoma/metabolism, Mice, Mice, Nude, Microphthalmia-Associated Transcription Factor/antagonists & inhibitors, Microphthalmia-Associated Transcription Factor/metabolism, RNA Interference, RNA, Small Interfering/metabolism, Recombinant Proteins/genetics, Recombinant Proteins/metabolism, Signal Transduction, Thiazolidinediones/therapeutic use, Transplantation, Heterologous
Pubmed
Web of science
Création de la notice
07/03/2013 16:50
Dernière modification de la notice
03/03/2018 19:19
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