Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of Inborn Errors of Metabolism and Screening |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942016000100404 |
Resumo: | Abstract Glycogen storage disease type 1 (GSD1) is an inherited disorder caused by impaired glucose 6-phosphatase activity. This impairment translates into the inhibition of endogenous glucose production and the subsequent accumulation of cellular glucose 6-phosphate. Excess glucose 6-phosphate enhances glycolysis, increases the production of fatty acids, uric acid, and lactate, causes hepatomegaly due to glycogen and lipid accumulation, and finally results in liver tumor development. Although the exact mechanisms of tumorigenesis in patients with GSD1 remain unclear, GSD1 hepatocytes undergo a Warburg-like metabolic switch. The consequent hyperactivation of specific metabolic pathways renders GSD1 hepatocytes susceptible to tumor development, presumably by providing the building blocks and energy required for cell proliferation. In addition to this, enhanced apoptosis in GSD1 may promote mitotic activity and hence result in DNA replication errors, thereby contributing to tumorigenesis. Increased carbohydrate responsive element-binding protein (ChREBP) and mammalian target of rapamycin (mTOR) activity and impaired AMP-activated protein kinase (AMPK) function likely play key roles in these pro-oncogenic processes. |
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Journal of Inborn Errors of Metabolism and Screening |
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Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environmentglycogen storage disease type 1steatosishepatocellular adenomas and carcinomascarcinogenesisglucose and lipid metabolismautophagyliverAbstract Glycogen storage disease type 1 (GSD1) is an inherited disorder caused by impaired glucose 6-phosphatase activity. This impairment translates into the inhibition of endogenous glucose production and the subsequent accumulation of cellular glucose 6-phosphate. Excess glucose 6-phosphate enhances glycolysis, increases the production of fatty acids, uric acid, and lactate, causes hepatomegaly due to glycogen and lipid accumulation, and finally results in liver tumor development. Although the exact mechanisms of tumorigenesis in patients with GSD1 remain unclear, GSD1 hepatocytes undergo a Warburg-like metabolic switch. The consequent hyperactivation of specific metabolic pathways renders GSD1 hepatocytes susceptible to tumor development, presumably by providing the building blocks and energy required for cell proliferation. In addition to this, enhanced apoptosis in GSD1 may promote mitotic activity and hence result in DNA replication errors, thereby contributing to tumorigenesis. Increased carbohydrate responsive element-binding protein (ChREBP) and mammalian target of rapamycin (mTOR) activity and impaired AMP-activated protein kinase (AMPK) function likely play key roles in these pro-oncogenic processes.Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT)2016-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942016000100404Journal of Inborn Errors of Metabolism and Screening v.4 2016reponame:Journal of Inborn Errors of Metabolism and Screeninginstname:Instituto Genética para Todos (IGPT)instacron:IGPT10.1177/2326409816679429info:eu-repo/semantics/openAccessGjorgjieva,MonikaOosterveer,Maaike H.Mithieux,GillesRajas,Fabienneeng2019-05-28T00:00:00Zoai:scielo:S2326-45942016000100404Revistahttp://jiems-journal.org/ONGhttps://old.scielo.br/oai/scielo-oai.phpjiems@jiems-journal.org||rgiugliani@hcpa.edu.br2326-45942326-4594opendoar:2019-05-28T00:00Journal of Inborn Errors of Metabolism and Screening - Instituto Genética para Todos (IGPT)false |
dc.title.none.fl_str_mv |
Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment |
title |
Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment |
spellingShingle |
Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment Gjorgjieva,Monika glycogen storage disease type 1 steatosis hepatocellular adenomas and carcinomas carcinogenesis glucose and lipid metabolism autophagy liver |
title_short |
Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment |
title_full |
Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment |
title_fullStr |
Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment |
title_full_unstemmed |
Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment |
title_sort |
Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment |
author |
Gjorgjieva,Monika |
author_facet |
Gjorgjieva,Monika Oosterveer,Maaike H. Mithieux,Gilles Rajas,Fabienne |
author_role |
author |
author2 |
Oosterveer,Maaike H. Mithieux,Gilles Rajas,Fabienne |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Gjorgjieva,Monika Oosterveer,Maaike H. Mithieux,Gilles Rajas,Fabienne |
dc.subject.por.fl_str_mv |
glycogen storage disease type 1 steatosis hepatocellular adenomas and carcinomas carcinogenesis glucose and lipid metabolism autophagy liver |
topic |
glycogen storage disease type 1 steatosis hepatocellular adenomas and carcinomas carcinogenesis glucose and lipid metabolism autophagy liver |
description |
Abstract Glycogen storage disease type 1 (GSD1) is an inherited disorder caused by impaired glucose 6-phosphatase activity. This impairment translates into the inhibition of endogenous glucose production and the subsequent accumulation of cellular glucose 6-phosphate. Excess glucose 6-phosphate enhances glycolysis, increases the production of fatty acids, uric acid, and lactate, causes hepatomegaly due to glycogen and lipid accumulation, and finally results in liver tumor development. Although the exact mechanisms of tumorigenesis in patients with GSD1 remain unclear, GSD1 hepatocytes undergo a Warburg-like metabolic switch. The consequent hyperactivation of specific metabolic pathways renders GSD1 hepatocytes susceptible to tumor development, presumably by providing the building blocks and energy required for cell proliferation. In addition to this, enhanced apoptosis in GSD1 may promote mitotic activity and hence result in DNA replication errors, thereby contributing to tumorigenesis. Increased carbohydrate responsive element-binding protein (ChREBP) and mammalian target of rapamycin (mTOR) activity and impaired AMP-activated protein kinase (AMPK) function likely play key roles in these pro-oncogenic processes. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942016000100404 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942016000100404 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1177/2326409816679429 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT) |
publisher.none.fl_str_mv |
Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT) |
dc.source.none.fl_str_mv |
Journal of Inborn Errors of Metabolism and Screening v.4 2016 reponame:Journal of Inborn Errors of Metabolism and Screening instname:Instituto Genética para Todos (IGPT) instacron:IGPT |
instname_str |
Instituto Genética para Todos (IGPT) |
instacron_str |
IGPT |
institution |
IGPT |
reponame_str |
Journal of Inborn Errors of Metabolism and Screening |
collection |
Journal of Inborn Errors of Metabolism and Screening |
repository.name.fl_str_mv |
Journal of Inborn Errors of Metabolism and Screening - Instituto Genética para Todos (IGPT) |
repository.mail.fl_str_mv |
jiems@jiems-journal.org||rgiugliani@hcpa.edu.br |
_version_ |
1754732519946715136 |