Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells

According to the stem cell theory for cancer, hepatocellular carcinomas are sustained by a group of cancer stem cells (CSCs) which are responsible for resistance to chemotherapy. In the present study we aimed to examine lipid metabolism in cancer stem cells induced by long-term treatment with sorafe...

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Autores: Bort Bueno, Alicia Carmen|||0000-0003-1490-5823, Sánchez Gómez, Belén|||0000-0003-0971-1522, Miguel García, Irene de|||0000-0002-3509-7813, Mateos Gómez, Pedro Antonio|||0000-0002-5539-2289, Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/60630
Acceso en línea:http://hdl.handle.net/10017/60630
https://dx.doi.org/10.1007/s11033-020-05352-3
Access Level:acceso abierto
Palabra clave:HepG2
Hepatocellular carcinoma
Huh7
Lipid metabolism
Sorafenib
cancer stem cells
Medicina
Medicine
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spelling Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cellsBort Bueno, Alicia Carmen|||0000-0003-1490-5823Sánchez Gómez, Belén|||0000-0003-0971-1522Miguel García, Irene de|||0000-0002-3509-7813Mateos Gómez, Pedro Antonio|||0000-0002-5539-2289Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373HepG2Hepatocellular carcinomaHuh7Lipid metabolismSorafenibcancer stem cellsMedicinaMedicineAccording to the stem cell theory for cancer, hepatocellular carcinomas are sustained by a group of cancer stem cells (CSCs) which are responsible for resistance to chemotherapy. In the present study we aimed to examine lipid metabolism in cancer stem cells induced by long-term treatment with sorafenib and its relationship with acquisition of a CSC-like phenotype. Two cell lines (HepG2SF1 and Huh7SF1) were generated by incubation with a step-wise increase of sorafenib concentrations for 10 months. These cell lines displayed stem-like characteristics like increase in the expression of ABCB1A, Nanog and Oct4 as well as an E-cadherin/N-cadherin switch. HepG2SF1 and Huh7SF1 cells showed intracellular accumulation of neutral lipids, assessed by flow cytometry and confocal microscopy. The exam of lipid metabolism revealed that HepG2SF1 and Huh7SF1 cells increased the expression of the enzymes involved in de novo lipid synthesis ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) and that of the fatty acid transporter CD36. In addition, these CSC-like cells had enhanced expression of the lipogenic transcription factor SREBP1c. Analysis of the key metabolic sensor AMP-activated kinase (AMPK) demonstrated that both AMPK phosphorylation and levels were decreased in the CSC-like cells compared to their parental cells. Interestingly, transfection of HepG2SF1 and Huh7SF1 cells with AMPK, restored the levels of the lipogenic enzymes and SREBP1c and decreased the intracellular lipid accumulation. Furthermore, AMPK transfection decreased the stemness markers and inhibited the E-cadherin/N-cadherin switch. Targeting AMPK and lipid metabolism of hepatocellular cancer stem cells is a promising strategy to face stemness and chemotherapy resistance.Fundación Tatiana Pérez de Guzmán el Bueno20202020-03-03journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/60630https://dx.doi.org/10.1007/s11033-020-05352-3reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/606302026-06-18T11:13:07Z
dc.title.none.fl_str_mv Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells
title Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells
spellingShingle Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells
Bort Bueno, Alicia Carmen|||0000-0003-1490-5823
HepG2
Hepatocellular carcinoma
Huh7
Lipid metabolism
Sorafenib
cancer stem cells
Medicina
Medicine
title_short Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells
title_full Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells
title_fullStr Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells
title_full_unstemmed Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells
title_sort Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells
dc.creator.none.fl_str_mv Bort Bueno, Alicia Carmen|||0000-0003-1490-5823
Sánchez Gómez, Belén|||0000-0003-0971-1522
Miguel García, Irene de|||0000-0002-3509-7813
Mateos Gómez, Pedro Antonio|||0000-0002-5539-2289
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author Bort Bueno, Alicia Carmen|||0000-0003-1490-5823
author_facet Bort Bueno, Alicia Carmen|||0000-0003-1490-5823
Sánchez Gómez, Belén|||0000-0003-0971-1522
Miguel García, Irene de|||0000-0002-3509-7813
Mateos Gómez, Pedro Antonio|||0000-0002-5539-2289
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author_role author
author2 Sánchez Gómez, Belén|||0000-0003-0971-1522
Miguel García, Irene de|||0000-0002-3509-7813
Mateos Gómez, Pedro Antonio|||0000-0002-5539-2289
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author2_role author
author
author
author
dc.subject.none.fl_str_mv HepG2
Hepatocellular carcinoma
Huh7
Lipid metabolism
Sorafenib
cancer stem cells
Medicina
Medicine
topic HepG2
Hepatocellular carcinoma
Huh7
Lipid metabolism
Sorafenib
cancer stem cells
Medicina
Medicine
description According to the stem cell theory for cancer, hepatocellular carcinomas are sustained by a group of cancer stem cells (CSCs) which are responsible for resistance to chemotherapy. In the present study we aimed to examine lipid metabolism in cancer stem cells induced by long-term treatment with sorafenib and its relationship with acquisition of a CSC-like phenotype. Two cell lines (HepG2SF1 and Huh7SF1) were generated by incubation with a step-wise increase of sorafenib concentrations for 10 months. These cell lines displayed stem-like characteristics like increase in the expression of ABCB1A, Nanog and Oct4 as well as an E-cadherin/N-cadherin switch. HepG2SF1 and Huh7SF1 cells showed intracellular accumulation of neutral lipids, assessed by flow cytometry and confocal microscopy. The exam of lipid metabolism revealed that HepG2SF1 and Huh7SF1 cells increased the expression of the enzymes involved in de novo lipid synthesis ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) and that of the fatty acid transporter CD36. In addition, these CSC-like cells had enhanced expression of the lipogenic transcription factor SREBP1c. Analysis of the key metabolic sensor AMP-activated kinase (AMPK) demonstrated that both AMPK phosphorylation and levels were decreased in the CSC-like cells compared to their parental cells. Interestingly, transfection of HepG2SF1 and Huh7SF1 cells with AMPK, restored the levels of the lipogenic enzymes and SREBP1c and decreased the intracellular lipid accumulation. Furthermore, AMPK transfection decreased the stemness markers and inhibited the E-cadherin/N-cadherin switch. Targeting AMPK and lipid metabolism of hepatocellular cancer stem cells is a promising strategy to face stemness and chemotherapy resistance.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-03-03
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10017/60630
https://dx.doi.org/10.1007/s11033-020-05352-3
url http://hdl.handle.net/10017/60630
https://dx.doi.org/10.1007/s11033-020-05352-3
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:e_Buah Biblioteca Digital Universidad de Alcalá
instname:Universidad de Alcalá (UAH)
instname_str Universidad de Alcalá (UAH)
reponame_str e_Buah Biblioteca Digital Universidad de Alcalá
collection e_Buah Biblioteca Digital Universidad de Alcalá
repository.name.fl_str_mv
repository.mail.fl_str_mv
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