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- Title
Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells.
- Authors
Bouaouiche, Sarra; Ghione, Silvia; Sghaier, Randa; Burgy, Olivier; Racoeur, Cindy; Derangère, Valentin; Bettaieb, Ali; Plenchette, Stéphanie
- Abstract
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.
- Subjects
TRIPLE-negative breast cancer; CANCER cells; NITROGLYCERIN; CARBOPLATIN; JAK-STAT pathway; CANCER cell migration; PROGNOSIS
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 16, p8449
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22168449