Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells

Autores
Antico Arciuch, Valeria Gabriela; Russo, Marika A.; Kang, Kristy S.; Di Cristofano, Antonio
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators.
Fil: Antico Arciuch, Valeria Gabriela. Albert Einstein College of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Russo, Marika A.. Albert Einstein College of Medicine; Estados Unidos
Fil: Kang, Kristy S.. Albert Einstein College of Medicine; Estados Unidos
Fil: Di Cristofano, Antonio. Albert Einstein College of Medicine; Estados Unidos
Materia
Tumorigenesis
Pten
Metabolism
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:11336/26300
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cellsAntico Arciuch, Valeria GabrielaRusso, Marika A.Kang, Kristy S.Di Cristofano, AntonioTumorigenesisPtenMetabolismhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators.Fil: Antico Arciuch, Valeria Gabriela. Albert Einstein College of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Russo, Marika A.. Albert Einstein College of Medicine; Estados UnidosFil: Kang, Kristy S.. Albert Einstein College of Medicine; Estados UnidosFil: Di Cristofano, Antonio. Albert Einstein College of Medicine; Estados UnidosAmerican Association for Cancer Research2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/26300Antico Arciuch, Valeria Gabriela; Russo, Marika A.; Kang, Kristy S.; Di Cristofano, Antonio; Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells; American Association for Cancer Research; Cancer Research; 73; 17; 9-2013; 5459-54720008-5472CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-13-1429info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/73/17/5459info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:39Zoai:ri.conicet.gov.ar:11336/26300instacron: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 09:55:40.136CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
title Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
spellingShingle Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
Antico Arciuch, Valeria Gabriela
Tumorigenesis
Pten
Metabolism
title_short Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
title_full Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
title_fullStr Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
title_full_unstemmed Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
title_sort Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
dc.creator.none.fl_str_mv Antico Arciuch, Valeria Gabriela
Russo, Marika A.
Kang, Kristy S.
Di Cristofano, Antonio
author Antico Arciuch, Valeria Gabriela
author_facet Antico Arciuch, Valeria Gabriela
Russo, Marika A.
Kang, Kristy S.
Di Cristofano, Antonio
author_role author
author2 Russo, Marika A.
Kang, Kristy S.
Di Cristofano, Antonio
author2_role author
author
author
dc.subject.none.fl_str_mv Tumorigenesis
Pten
Metabolism
topic Tumorigenesis
Pten
Metabolism
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators.
Fil: Antico Arciuch, Valeria Gabriela. Albert Einstein College of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Russo, Marika A.. Albert Einstein College of Medicine; Estados Unidos
Fil: Kang, Kristy S.. Albert Einstein College of Medicine; Estados Unidos
Fil: Di Cristofano, Antonio. Albert Einstein College of Medicine; Estados Unidos
description Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
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/11336/26300
Antico Arciuch, Valeria Gabriela; Russo, Marika A.; Kang, Kristy S.; Di Cristofano, Antonio; Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells; American Association for Cancer Research; Cancer Research; 73; 17; 9-2013; 5459-5472
0008-5472
CONICET Digital
CONICET
url http://hdl.handle.net/11336/26300
identifier_str_mv Antico Arciuch, Valeria Gabriela; Russo, Marika A.; Kang, Kristy S.; Di Cristofano, Antonio; Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells; American Association for Cancer Research; Cancer Research; 73; 17; 9-2013; 5459-5472
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/doi/10.1158/0008-5472.CAN-13-1429
info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/73/17/5459
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_ 1842269358935506944
score 13.13397

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