Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma
Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myelo...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/7/1662 |
| _version_ | 1797539110848561152 |
|---|---|
| author | Alejandra Ortiz-Ruiz Yanira Ruiz-Heredia María Luz Morales Pedro Aguilar-Garrido Almudena García-Ortiz Antonio Valeri Carmen Bárcena Rosa María García-Martin Vanesa Garrido Laura Moreno Alicia Gimenez Miguel Ángel Navarro-Aguadero María Velasco-Estevez Eva Lospitao María Teresa Cedena Santiago Barrio Joaquín Martínez-López María Linares Miguel Gallardo |
| author_facet | Alejandra Ortiz-Ruiz Yanira Ruiz-Heredia María Luz Morales Pedro Aguilar-Garrido Almudena García-Ortiz Antonio Valeri Carmen Bárcena Rosa María García-Martin Vanesa Garrido Laura Moreno Alicia Gimenez Miguel Ángel Navarro-Aguadero María Velasco-Estevez Eva Lospitao María Teresa Cedena Santiago Barrio Joaquín Martínez-López María Linares Miguel Gallardo |
| author_sort | Alejandra Ortiz-Ruiz |
| collection | DOAJ |
| description | Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities. |
| first_indexed | 2024-03-10T12:40:39Z |
| format | Article |
| id | doaj.art-6c9dbe3ba6814caf9ec2f6cc29b1bd3a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:40:39Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6c9dbe3ba6814caf9ec2f6cc29b1bd3a2023-11-21T13:52:42ZengMDPI AGCancers2072-66942021-04-01137166210.3390/cancers13071662Myc-Related Mitochondrial Activity as a Novel Target for Multiple MyelomaAlejandra Ortiz-Ruiz0Yanira Ruiz-Heredia1María Luz Morales2Pedro Aguilar-Garrido3Almudena García-Ortiz4Antonio Valeri5Carmen Bárcena6Rosa María García-Martin7Vanesa Garrido8Laura Moreno9Alicia Gimenez10Miguel Ángel Navarro-Aguadero11María Velasco-Estevez12Eva Lospitao13María Teresa Cedena14Santiago Barrio15Joaquín Martínez-López16María Linares17Miguel Gallardo18H12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainPathology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainPathology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainCNIO–Lilly Cell Signalling and Immunometabolism Section, CNIO, 28029 Madrid, SpainHematology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainH12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, SpainMitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.https://www.mdpi.com/2072-6694/13/7/1662multiple myelomamitochondriatigecyclineMYC |
| spellingShingle | Alejandra Ortiz-Ruiz Yanira Ruiz-Heredia María Luz Morales Pedro Aguilar-Garrido Almudena García-Ortiz Antonio Valeri Carmen Bárcena Rosa María García-Martin Vanesa Garrido Laura Moreno Alicia Gimenez Miguel Ángel Navarro-Aguadero María Velasco-Estevez Eva Lospitao María Teresa Cedena Santiago Barrio Joaquín Martínez-López María Linares Miguel Gallardo Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma Cancers multiple myeloma mitochondria tigecycline MYC |
| title | Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma |
| title_full | Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma |
| title_fullStr | Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma |
| title_full_unstemmed | Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma |
| title_short | Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma |
| title_sort | myc related mitochondrial activity as a novel target for multiple myeloma |
| topic | multiple myeloma mitochondria tigecycline MYC |
| url | https://www.mdpi.com/2072-6694/13/7/1662 |
| work_keys_str_mv | AT alejandraortizruiz mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT yaniraruizheredia mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT marialuzmorales mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT pedroaguilargarrido mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT almudenagarciaortiz mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT antoniovaleri mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT carmenbarcena mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT rosamariagarciamartin mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT vanesagarrido mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT lauramoreno mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT aliciagimenez mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT miguelangelnavarroaguadero mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT mariavelascoestevez mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT evalospitao mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT mariateresacedena mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT santiagobarrio mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT joaquinmartinezlopez mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT marialinares mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma AT miguelgallardo mycrelatedmitochondrialactivityasanoveltargetformultiplemyeloma |