Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells.
Fiche publication
Date publication
août 2021
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BETTAIEB Ali, Dr PLENCHETTE Stéphanie, Dr DERANGERE Valentin
Tous les auteurs :
Bouaouiche S, Ghione S, Sghaier R, Burgy O, Racoeur C, Derangère V, Bettaieb A, Plenchette S
Lien Pubmed
Résumé
Triple-negative breast cancer (TNBC) is a highly aggressive disease with invasive and metastasizing properties associated with a poor prognosis. The STAT3 signaling pathway has shown a pivotal role in cancer cell migration, invasion, metastasis and drug resistance of TNBC cells. IL-6 is a main upstream activator of the JAK2/STAT3 pathway. In the present study we examined the impact of the NO-donor glyceryl trinitrate (GTN) on the activation of the JAK2/STAT3 signaling pathway and subsequent migration, invasion and metastasis ability of TNBC cells through in vitro and in vivo experiments. We used a subtoxic dose of carboplatin and/or recombinant IL-6 to activate the JAK2/STAT3 signaling pathway and its functional outcomes. We found an inhibitory effect of GTN on the activation of the JAK2/STAT3 signaling, migration and invasion of TNBC cells. We discovered that GTN inhibits the activation of JAK2, the upstream activator of STAT3, and mediates the S-nitrosylation of JAK2. Finally, the effect of GTN (Nitronal) on lung metastasis was investigated to assess its antitumor activity in vivo.
Mots clés
cancer, invasion, metastasis, migration, nitric oxide, signaling
Référence
Int J Mol Sci. 2021 Aug 6;22(16):