AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer

Autores
Priolo, Carmen; Pyne, Saumyadipta; Rose, Joshua; Regan, Erzsébet Ravasz; Zadra, Giorgia; Photopoulos, Cornelia; Cacciatore, Stefano; Schultz, Denise; Scaglia, Natalia; McDunn, Jonathan; de Marzo, Angelo M.; Loda, Massimo
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry–based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our findings show how prostate tumors undergo a metabolic reprogramming that reflects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.
Fil: Priolo, Carmen. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Pyne, Saumyadipta. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Rose, Joshua. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Regan, Erzsébet Ravasz. Harvard Medical School; Estados Unidos
Fil: Zadra, Giorgia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Photopoulos, Cornelia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Cacciatore, Stefano. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Schultz, Denise. Johns Hopkins University; Estados Unidos
Fil: Scaglia, Natalia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: McDunn, Jonathan. Metabolon Inc.; Estados Unidos
Fil: de Marzo, Angelo M.. Johns Hopkins University; Estados Unidos
Fil: Loda, Massimo. Department of Pathology. Brigham and Women's Hospital; Estados Unidos. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos. University of Cambridge; Estados Unidos. King's College London. Division of Cancer Studies; Estados Unidos
Materia
AKT
MYC
METABOLISM
PROSTATE CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/102936
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/102936
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate CancerPriolo, CarmenPyne, SaumyadiptaRose, JoshuaRegan, Erzsébet RavaszZadra, GiorgiaPhotopoulos, CorneliaCacciatore, StefanoSchultz, DeniseScaglia, NataliaMcDunn, Jonathande Marzo, Angelo M.Loda, MassimoAKTMYCMETABOLISMPROSTATE CANCERhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry–based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our findings show how prostate tumors undergo a metabolic reprogramming that reflects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.Fil: Priolo, Carmen. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Pyne, Saumyadipta. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Rose, Joshua. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Regan, Erzsébet Ravasz. Harvard Medical School; Estados UnidosFil: Zadra, Giorgia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Photopoulos, Cornelia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Cacciatore, Stefano. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Schultz, Denise. Johns Hopkins University; Estados UnidosFil: Scaglia, Natalia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: McDunn, Jonathan. Metabolon Inc.; Estados UnidosFil: de Marzo, Angelo M.. Johns Hopkins University; Estados UnidosFil: Loda, Massimo. Department of Pathology. Brigham and Women's Hospital; Estados Unidos. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos. University of Cambridge; Estados Unidos. King's College London. Division of Cancer Studies; Estados UnidosAmerican Association for Cancer Research2014-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/102936Priolo, Carmen; Pyne, Saumyadipta; Rose, Joshua; Regan, Erzsébet Ravasz; Zadra, Giorgia; et al.; AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer; American Association for Cancer Research; Cancer Research; 74; 24; 12-2014; 7198-72040008-5472CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://cancerres.aacrjournals.org/content/74/24/7198info:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-14-1490info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:35Zoai:ri.conicet.gov.ar:11336/102936instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:55:35.737CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer
title AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer
spellingShingle AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer
Priolo, Carmen
AKT
MYC
METABOLISM
PROSTATE CANCER
title_short AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer
title_full AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer
title_fullStr AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer
title_full_unstemmed AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer
title_sort AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer
dc.creator.none.fl_str_mv Priolo, Carmen
Pyne, Saumyadipta
Rose, Joshua
Regan, Erzsébet Ravasz
Zadra, Giorgia
Photopoulos, Cornelia
Cacciatore, Stefano
Schultz, Denise
Scaglia, Natalia
McDunn, Jonathan
de Marzo, Angelo M.
Loda, Massimo
author Priolo, Carmen
author_facet Priolo, Carmen
Pyne, Saumyadipta
Rose, Joshua
Regan, Erzsébet Ravasz
Zadra, Giorgia
Photopoulos, Cornelia
Cacciatore, Stefano
Schultz, Denise
Scaglia, Natalia
McDunn, Jonathan
de Marzo, Angelo M.
Loda, Massimo
author_role author
author2 Pyne, Saumyadipta
Rose, Joshua
Regan, Erzsébet Ravasz
Zadra, Giorgia
Photopoulos, Cornelia
Cacciatore, Stefano
Schultz, Denise
Scaglia, Natalia
McDunn, Jonathan
de Marzo, Angelo M.
Loda, Massimo
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AKT
MYC
METABOLISM
PROSTATE CANCER
topic AKT
MYC
METABOLISM
PROSTATE CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry–based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our findings show how prostate tumors undergo a metabolic reprogramming that reflects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.
Fil: Priolo, Carmen. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Pyne, Saumyadipta. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Rose, Joshua. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Regan, Erzsébet Ravasz. Harvard Medical School; Estados Unidos
Fil: Zadra, Giorgia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Photopoulos, Cornelia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Cacciatore, Stefano. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos
Fil: Schultz, Denise. Johns Hopkins University; Estados Unidos
Fil: Scaglia, Natalia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: McDunn, Jonathan. Metabolon Inc.; Estados Unidos
Fil: de Marzo, Angelo M.. Johns Hopkins University; Estados Unidos
Fil: Loda, Massimo. Department of Pathology. Brigham and Women's Hospital; Estados Unidos. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos. University of Cambridge; Estados Unidos. King's College London. Division of Cancer Studies; Estados Unidos
description Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry–based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our findings show how prostate tumors undergo a metabolic reprogramming that reflects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.
publishDate 2014
dc.date.none.fl_str_mv 2014-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/102936
Priolo, Carmen; Pyne, Saumyadipta; Rose, Joshua; Regan, Erzsébet Ravasz; Zadra, Giorgia; et al.; AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer; American Association for Cancer Research; Cancer Research; 74; 24; 12-2014; 7198-7204
0008-5472
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102936
identifier_str_mv Priolo, Carmen; Pyne, Saumyadipta; Rose, Joshua; Regan, Erzsébet Ravasz; Zadra, Giorgia; et al.; AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer; American Association for Cancer Research; Cancer Research; 74; 24; 12-2014; 7198-7204
0008-5472
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://cancerres.aacrjournals.org/content/74/24/7198
info:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-14-1490
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269353769172992
score 13.13397

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