Metabolic genes in hepatocellular carcinoma developement

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 08-09-2016

Detalhes bibliográficos
Autor: Manieri, Elisa
Tipo de documento: tese
Data de publicação:2016
País:España
Recursos:Universidad Autónoma de Madrid
Repositório:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:espanhol
inglês
OAI Identifier:oai:repositorio.uam.es:10486/675017
Acesso em linha:http://hdl.handle.net/10486/675017
Access Level:Acceso aberto
Palavra-chave:Hígado - Cáncer - Tesis doctorales
Biología y Biomedicina / Biología
id ES_73473cedeb17b71a011af7b65db6b918
oai_identifier_str oai:repositorio.uam.es:10486/675017
network_acronym_str ES
network_name_str España
repository_id_str
spelling Metabolic genes in hepatocellular carcinoma developementManieri, ElisaHígado - Cáncer - Tesis doctoralesBiología y Biomedicina / BiologíaTesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 08-09-2016Esta tesis tiene embargado el acceso al texto completo hasta el 09-09-2018Hepatocellular carcinoma (HCC) is the second leading cause of death for cancer worldwide. Several studies on hepatocellular carcinoma epidemiology linked this malignancy with obesity and metabolic disorders. However, little is known about the molecular mechanisms responsible for this connection. The main purpose of this thesis is to elucidate the role of Jnk1 and Ppara, two important metabolic genes, in hepatocellular carcinoma development. Adipose tissue is the most important organ for lipid storage; during obesity it undergoes to a substantial remodeling. JNK1 is known to control IL-6 production in the adipose tissue during obesity and its depletion in adipocyte protects against liver steatosis, a predisposing factor for HCC development. We demonstrate that adipose tissue JNK1 in normal diet can trigger hepatocellular carcinoma development. In fact, the deletion of JNK1 in adipose tissue increases circulating levels of adiponectin, which in turn activates AMPKα and p38α in hepatocytes, protecting against chemical-induced tumor development. Our results highlight the relevance of adipose tissue in liver cancer development and the central role that JNK1 plays in this crosstalk. PPARα is a nuclear receptor of fatty acids. It is highly expressed in the liver and obesity induces its activation. However, PPARα role in liver carcinogenesis is controversial. Here we show that PPARα activation promotes obesity-associated hepatic cancer. Mice lacking PPARα are protected against chemical-induced hepatocellular carcinoma when fed a high fat diet. Additionally, bone marrow transplantation experiments reveal no significant contribution of inflammatory cells, suggesting a cell-autonomous function of PPARα in hepatocytes. Hepatic PPARα activation, induced by Jnk1 and Jnk2 deletion, is sufficient to cause spontaneous liver cancer, confirming a central role of PPARα activation in liver tumorigenesis. Our results provide a molecular mechanism linking metabolic disorders with liver cancer, emphasizing a central role for PPARα in the connectionThe support received from the following Grants and Fellowships has permitted to develop this PhD work: La Caixa International PhD Fellowship Program, 2010 CallSabio-Buzo, GuadalupeDepartamento de Biología MolecularFacultad de CienciasCentro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) CSIC. Centro Nacional de Biotecnología (CNB)20162016-09-08doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/675017reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridEspañolspaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6750172026-06-23T12:46:27Z
dc.title.none.fl_str_mv Metabolic genes in hepatocellular carcinoma developement
title Metabolic genes in hepatocellular carcinoma developement
spellingShingle Metabolic genes in hepatocellular carcinoma developement
Manieri, Elisa
Hígado - Cáncer - Tesis doctorales
Biología y Biomedicina / Biología
title_short Metabolic genes in hepatocellular carcinoma developement
title_full Metabolic genes in hepatocellular carcinoma developement
title_fullStr Metabolic genes in hepatocellular carcinoma developement
title_full_unstemmed Metabolic genes in hepatocellular carcinoma developement
title_sort Metabolic genes in hepatocellular carcinoma developement
dc.creator.none.fl_str_mv Manieri, Elisa
author Manieri, Elisa
author_facet Manieri, Elisa
author_role author
dc.contributor.none.fl_str_mv Sabio-Buzo, Guadalupe
Departamento de Biología Molecular
Facultad de Ciencias
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) 
CSIC. Centro Nacional de Biotecnología (CNB)
dc.subject.none.fl_str_mv Hígado - Cáncer - Tesis doctorales
Biología y Biomedicina / Biología
topic Hígado - Cáncer - Tesis doctorales
Biología y Biomedicina / Biología
description Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 08-09-2016
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-09-08
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/675017
url http://hdl.handle.net/10486/675017
dc.language.none.fl_str_mv Español
spa
Inglés
eng
language_invalid_str_mv Español
Inglés
language spa
eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410797696843776
score 15,301603

Registros relacionados