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dc.contributor.author
Zadra, Giorgia
dc.contributor.author
Photopoulos, Cornelia
dc.contributor.author
Tyekucheva, Svitlana
dc.contributor.author
Heidari, Pedram
dc.contributor.author
Weng, Qing Ping
dc.contributor.author
Fedele, Giuseppe
dc.contributor.author
Liu, Hong
dc.contributor.author
Scaglia, Natalia
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dc.contributor.author
Priolo, Carmen
dc.contributor.author
Sicinska, Ewa
dc.contributor.author
Mahmood, Umar
dc.contributor.author
Signoretti, Sabina
dc.contributor.author
Birnberg, Neal
dc.contributor.author
Loda, Massimo
dc.date.available
2020-04-03T17:29:43Z
dc.date.issued
2014-02
dc.identifier.citation
Zadra, Giorgia; Photopoulos, Cornelia; Tyekucheva, Svitlana; Heidari, Pedram; Weng, Qing Ping; et al.; A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis; Wiley Blackwell Publishing, Inc; Embo Molecular Medicine; 6; 4; 2-2014; 519-538
dc.identifier.issn
1757-4676
dc.identifier.uri
http://hdl.handle.net/11336/101867
dc.description.abstract
5´AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth remains to be determined. A small molecule screening was performed and identified MT 63-78, a specific and potent direct AMPK activator. Here, we show that direct activation of AMPK inhibits PCa cell growth in androgen sensitive and castration resistant PCa (CRPC) models, induces mitotic arrest, and apoptosis. In vivo, AMPK activation is sufficient to reduce PCa growth, whereas the allelic loss of its catalytic subunits fosters PCa development. Importantly, despite mTORC1 blockade, the suppression of de novo lipogenesis is the underpinning mechanism responsible for AMPK-mediated PCa growth inhibition, suggesting AMPK as a therapeutic target especially for lipogenesis-driven PCas. Finally, we demonstrate that MT 63-78 enhances the growth inhibitory effect of AR signaling inhibitors MDV3100 and abiraterone. This study thus provides a rationale for their combined use in CRPC treatment.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley Blackwell Publishing, Inc
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dc.relation
Corregido en https://doi.org/10.15252/emmm.201470070
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
AMPK DIRECT ACTIVATION
dc.subject
ANDROGEN SIGNALING INHIBITORS
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DE NOVO LIPOGENESIS
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PROSTATE CANCER
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-04-02T15:17:03Z
dc.identifier.eissn
1757-4684
dc.journal.volume
6
dc.journal.number
4
dc.journal.pagination
519-538
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Zadra, Giorgia. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Photopoulos, Cornelia. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Tyekucheva, Svitlana. Harvard University. Harvard School of Public Health; Estados Unidos. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Heidari, Pedram. Massachusetts General Hospital; Estados Unidos
dc.description.fil
Fil: Weng, Qing Ping. Mercury Pharmaceuticals; Estados Unidos
dc.description.fil
Fil: Fedele, Giuseppe. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Liu, Hong. Mercury Pharmaceuticals; Estados Unidos
dc.description.fil
Fil: Scaglia, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Priolo, Carmen. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Sicinska, Ewa. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Mahmood, Umar. Massachusetts General Hospital; Estados Unidos
dc.description.fil
Fil: Signoretti, Sabina. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Birnberg, Neal. Mercury Pharmaceuticals; Estados Unidos
dc.description.fil
Fil: Loda, Massimo. Harvard Medical School; Estados Unidos. King’s College London; Reino Unido. The Broad Institute; Estados Unidos
dc.journal.title
Embo Molecular Medicine
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/emmm.201302734
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.embopress.org/doi/full/10.1002/emmm.201302734
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