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dc.contributor.author
Antico Arciuch, Valeria Gabriela
dc.contributor.author
Russo, Marika A.
dc.contributor.author
Kang, Kristy S.
dc.contributor.author
Di Cristofano, Antonio
dc.date.available
2017-10-09T21:07:36Z
dc.date.issued
2013-09
dc.identifier.citation
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
dc.identifier.issn
0008-5472
dc.identifier.uri
http://hdl.handle.net/11336/26300
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Association for Cancer Research
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Tumorigenesis
dc.subject
Pten
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Metabolism
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Inhibition of AMPK and Krebs Cycle Gene expression drives metabolic remodeling of Pten-Deficient Preneoplastic thyroid cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-10-06T18:56:59Z
dc.journal.volume
73
dc.journal.number
17
dc.journal.pagination
5459-5472
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Antico Arciuch, Valeria Gabriela. Albert Einstein College of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Russo, Marika A.. Albert Einstein College of Medicine; Estados Unidos
dc.description.fil
Fil: Kang, Kristy S.. Albert Einstein College of Medicine; Estados Unidos
dc.description.fil
Fil: Di Cristofano, Antonio. Albert Einstein College of Medicine; Estados Unidos
dc.journal.title
Cancer Research
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1158/0008-5472.CAN-13-1429
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/73/17/5459


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