Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells
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 upstr...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/16/8449 |
| _version_ | 1797523613152182272 |
|---|---|
| author | Sarra Bouaouiche Silvia Ghione Randa Sghaier Olivier Burgy Cindy Racoeur Valentin Derangère Ali Bettaieb Stéphanie Plenchette |
| author_facet | Sarra Bouaouiche Silvia Ghione Randa Sghaier Olivier Burgy Cindy Racoeur Valentin Derangère Ali Bettaieb Stéphanie Plenchette |
| author_sort | Sarra Bouaouiche |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:45:30Z |
| format | Article |
| id | doaj.art-16a1d7fffb4e4bd9bd0e48aef8a63fc3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:45:30Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-16a1d7fffb4e4bd9bd0e48aef8a63fc32023-11-22T07:55:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216844910.3390/ijms22168449Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer CellsSarra Bouaouiche0Silvia Ghione1Randa Sghaier2Olivier Burgy3Cindy Racoeur4Valentin Derangère5Ali Bettaieb6Stéphanie Plenchette7Laboratoire d’Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75000 Paris, FranceLaboratoire d’Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75000 Paris, FranceLaboratoire d’Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75000 Paris, FranceINSERM U1231, UFR Sciences de Santé, Université de Bourgogne-Franche Comté, 21000 Dijon, FranceLaboratoire d’Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75000 Paris, FrancePlateforme de Transfert en Biologie du Cancer, Centre Georges-François Leclerc, 21000 Dijon, FranceLaboratoire d’Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75000 Paris, FranceLaboratoire d’Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75000 Paris, FranceTriple-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.https://www.mdpi.com/1422-0067/22/16/8449cancernitric oxidesignalingmigrationinvasionmetastasis |
| spellingShingle | Sarra Bouaouiche Silvia Ghione Randa Sghaier Olivier Burgy Cindy Racoeur Valentin Derangère Ali Bettaieb Stéphanie Plenchette Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells International Journal of Molecular Sciences cancer nitric oxide signaling migration invasion metastasis |
| title | Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells |
| title_full | Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells |
| title_fullStr | Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells |
| title_full_unstemmed | Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells |
| title_short | Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells |
| title_sort | nitric oxide releasing drug glyceryl trinitrate targets jak2 stat3 signaling migration and invasion of triple negative breast cancer cells |
| topic | cancer nitric oxide signaling migration invasion metastasis |
| url | https://www.mdpi.com/1422-0067/22/16/8449 |
| work_keys_str_mv | AT sarrabouaouiche nitricoxidereleasingdrugglyceryltrinitratetargetsjak2stat3signalingmigrationandinvasionoftriplenegativebreastcancercells AT silviaghione nitricoxidereleasingdrugglyceryltrinitratetargetsjak2stat3signalingmigrationandinvasionoftriplenegativebreastcancercells AT randasghaier nitricoxidereleasingdrugglyceryltrinitratetargetsjak2stat3signalingmigrationandinvasionoftriplenegativebreastcancercells AT olivierburgy nitricoxidereleasingdrugglyceryltrinitratetargetsjak2stat3signalingmigrationandinvasionoftriplenegativebreastcancercells AT cindyracoeur nitricoxidereleasingdrugglyceryltrinitratetargetsjak2stat3signalingmigrationandinvasionoftriplenegativebreastcancercells AT valentinderangere nitricoxidereleasingdrugglyceryltrinitratetargetsjak2stat3signalingmigrationandinvasionoftriplenegativebreastcancercells AT alibettaieb nitricoxidereleasingdrugglyceryltrinitratetargetsjak2stat3signalingmigrationandinvasionoftriplenegativebreastcancercells AT stephanieplenchette nitricoxidereleasingdrugglyceryltrinitratetargetsjak2stat3signalingmigrationandinvasionoftriplenegativebreastcancercells |