Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids

Ruiz-de-Gauna, M. (Mikel)|||/items/b3fdb2fe-141e-4e66-b98f-339736cf9274; Biancaniello, F. (Francesca)|||/items/d465cfda-d22e-46c9-9920-7558b1efb8b0; González-Romero, F. (Francisco)|||/items/27f57966-25e7-4089-9bb5-9cfcbc5747a2; Rodrigues, P.M. (Pedro M.)|||/items/b2eb48c0-8f5b-4ce3-8fa7-330864e4c609; Lapitz, A. (Ainhoa)|||/items/3ca2b075-145a-4acd-ae22-d52246e4778f; Gómez-Santos, B. (Beatriz)|||/items/426fd680-44c0-4bb1-8f75-aec188bd070b; Olaizola, P. (Paula)|||/items/5426b4b4-4ac7-46f7-8304-17cb549c08a4; Matteo, S. (Sabina) Di|||/items/067048b7-7419-4424-a836-e1d3acbd2c27; Aurrekoetxea, I. (Igor)|||/items/c109bf8d-7a3b-4b75-9cd6-05bc5e62331f; Labiano, I. (Ibone)|||/items/184c5ecc-80d3-4326-afc1-93295ec4ba66; Nieva-Zuluaga, A. (Ane)|||/items/5af56c2d-2f4c-4e29-8d04-4a95e9165960; Benito-Vicente, A. (Asier)|||/items/7827ee97-7b23-4456-a626-f950ea74fcc1; Perugorria, M.J. (María J.)|||/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9; Apodaka-Biguri, M. (Maider)|||/items/14dbc28a-065f-40f6-9706-a34517e83351; Paiva, N.A. (Nuno A.)|||/items/8df71801-9888-4874-bdf6-6c956af0b3a0; Saenz-De-Urturi, D. (Diego)|||/items/9cae7551-eaae-49fd-a0f2-ee63e52246e5; Buque, X. (Xabier)|||/items/dac3924e-8d31-4515-9e76-f46cc41c0acc; Delgado, I. (Igotz)|||/items/2fa21136-56fe-424e-81a8-67c78ab6b648; Martín, C. (Cesar)|||/items/86a97a3c-cf22-4c98-b915-e085b2cfeb92; Azkargorta, M. (Mikel)|||/items/3411ce9e-9088-4b6c-b9f2-4b055b8ef982; Elortza, F. (Felix)|||/items/b59cc8e8-12c0-448a-91fc-ef330149f608; Calvisi, D.F. (Diego F.)|||/items/f1fd12a7-edff-43c9-a8a8-425bd3a0d865; Andersen, J.B. (Jesper B.)|||/items/30522278-e252-4feb-9558-84b5c027103a; Alvaro, D. (Domenico)|||/items/f9c14989-1042-4c59-a9b3-fd2c47c86939; Cardinale, V. (Vincenzo)|||/items/04ce3ed2-9b97-481b-87f3-b062ad49057d; Bujanda, L. (Luis)|||/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85; Banales, J.M. (Jesús M.)|||/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5; Aspichueta, P. (Patricia)|||/items/384763a9-5584-4c74-baec-92991a901d35

Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids

Background and aims: Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with a dismal prognosis. We investigated if lipid metabolism is disrupted in CCA and its role in tumor proliferation. Approach and results: The in vitro and in vivo tumorigenic capacity of five human CCA...

Descripción completa

Detalles Bibliográficos
Autores:	Ruiz-de-Gauna, M. (Mikel)\|\|\|/items/b3fdb2fe-141e-4e66-b98f-339736cf9274, Biancaniello, F. (Francesca)\|\|\|/items/d465cfda-d22e-46c9-9920-7558b1efb8b0, González-Romero, F. (Francisco)\|\|\|/items/27f57966-25e7-4089-9bb5-9cfcbc5747a2, Rodrigues, P.M. (Pedro M.)\|\|\|/items/b2eb48c0-8f5b-4ce3-8fa7-330864e4c609, Lapitz, A. (Ainhoa)\|\|\|/items/3ca2b075-145a-4acd-ae22-d52246e4778f, Gómez-Santos, B. (Beatriz)\|\|\|/items/426fd680-44c0-4bb1-8f75-aec188bd070b, Olaizola, P. (Paula)\|\|\|/items/5426b4b4-4ac7-46f7-8304-17cb549c08a4, Matteo, S. (Sabina) Di\|\|\|/items/067048b7-7419-4424-a836-e1d3acbd2c27, Aurrekoetxea, I. (Igor)\|\|\|/items/c109bf8d-7a3b-4b75-9cd6-05bc5e62331f, Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66, Nieva-Zuluaga, A. (Ane)\|\|\|/items/5af56c2d-2f4c-4e29-8d04-4a95e9165960, Benito-Vicente, A. (Asier)\|\|\|/items/7827ee97-7b23-4456-a626-f950ea74fcc1, Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9, Apodaka-Biguri, M. (Maider)\|\|\|/items/14dbc28a-065f-40f6-9706-a34517e83351, Paiva, N.A. (Nuno A.)\|\|\|/items/8df71801-9888-4874-bdf6-6c956af0b3a0, Saenz-De-Urturi, D. (Diego)\|\|\|/items/9cae7551-eaae-49fd-a0f2-ee63e52246e5, Buque, X. (Xabier)\|\|\|/items/dac3924e-8d31-4515-9e76-f46cc41c0acc, Delgado, I. (Igotz)\|\|\|/items/2fa21136-56fe-424e-81a8-67c78ab6b648, Martín, C. (Cesar)\|\|\|/items/86a97a3c-cf22-4c98-b915-e085b2cfeb92, Azkargorta, M. (Mikel)\|\|\|/items/3411ce9e-9088-4b6c-b9f2-4b055b8ef982, Elortza, F. (Felix)\|\|\|/items/b59cc8e8-12c0-448a-91fc-ef330149f608, Calvisi, D.F. (Diego F.)\|\|\|/items/f1fd12a7-edff-43c9-a8a8-425bd3a0d865, Andersen, J.B. (Jesper B.)\|\|\|/items/30522278-e252-4feb-9558-84b5c027103a, Alvaro, D. (Domenico)\|\|\|/items/f9c14989-1042-4c59-a9b3-fd2c47c86939, Cardinale, V. (Vincenzo)\|\|\|/items/04ce3ed2-9b97-481b-87f3-b062ad49057d, Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85, Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5, Aspichueta, P. (Patricia)\|\|\|/items/384763a9-5584-4c74-baec-92991a901d35
Tipo de recurso:	artículo
Fecha de publicación:	2022
País:	España
Institución:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:	inglés
OAI Identifier:	oai:dadun.unav.edu:10171/119012
Acceso en línea:	https://hdl.handle.net/10171/119012
Access Level:	acceso abierto
Palabra clave:	Cholangiocarcinoma Biliary cancers Dismal prognosis Lipid metabolism

id	ES_c9fcfeac8be6ae0d1fee44fbd63ba191
oai_identifier_str	oai:dadun.unav.edu:10171/119012
network_acronym_str	ES
network_name_str	España
repository_id_str
dc.title.none.fl_str_mv	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids
title	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids
spellingShingle	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids Ruiz-de-Gauna, M. (Mikel)\|\|\|/items/b3fdb2fe-141e-4e66-b98f-339736cf9274 Cholangiocarcinoma Biliary cancers Dismal prognosis Lipid metabolism
title_short	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids
title_full	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids
title_fullStr	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids
title_full_unstemmed	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids
title_sort	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids
dc.creator.none.fl_str_mv	Ruiz-de-Gauna, M. (Mikel)\|\|\|/items/b3fdb2fe-141e-4e66-b98f-339736cf9274 Biancaniello, F. (Francesca)\|\|\|/items/d465cfda-d22e-46c9-9920-7558b1efb8b0 González-Romero, F. (Francisco)\|\|\|/items/27f57966-25e7-4089-9bb5-9cfcbc5747a2 Rodrigues, P.M. (Pedro M.)\|\|\|/items/b2eb48c0-8f5b-4ce3-8fa7-330864e4c609 Lapitz, A. (Ainhoa)\|\|\|/items/3ca2b075-145a-4acd-ae22-d52246e4778f Gómez-Santos, B. (Beatriz)\|\|\|/items/426fd680-44c0-4bb1-8f75-aec188bd070b Olaizola, P. (Paula)\|\|\|/items/5426b4b4-4ac7-46f7-8304-17cb549c08a4 Matteo, S. (Sabina) Di\|\|\|/items/067048b7-7419-4424-a836-e1d3acbd2c27 Aurrekoetxea, I. (Igor)\|\|\|/items/c109bf8d-7a3b-4b75-9cd6-05bc5e62331f Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66 Nieva-Zuluaga, A. (Ane)\|\|\|/items/5af56c2d-2f4c-4e29-8d04-4a95e9165960 Benito-Vicente, A. (Asier)\|\|\|/items/7827ee97-7b23-4456-a626-f950ea74fcc1 Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9 Apodaka-Biguri, M. (Maider)\|\|\|/items/14dbc28a-065f-40f6-9706-a34517e83351 Paiva, N.A. (Nuno A.)\|\|\|/items/8df71801-9888-4874-bdf6-6c956af0b3a0 Saenz-De-Urturi, D. (Diego)\|\|\|/items/9cae7551-eaae-49fd-a0f2-ee63e52246e5 Buque, X. (Xabier)\|\|\|/items/dac3924e-8d31-4515-9e76-f46cc41c0acc Delgado, I. (Igotz)\|\|\|/items/2fa21136-56fe-424e-81a8-67c78ab6b648 Martín, C. (Cesar)\|\|\|/items/86a97a3c-cf22-4c98-b915-e085b2cfeb92 Azkargorta, M. (Mikel)\|\|\|/items/3411ce9e-9088-4b6c-b9f2-4b055b8ef982 Elortza, F. (Felix)\|\|\|/items/b59cc8e8-12c0-448a-91fc-ef330149f608 Calvisi, D.F. (Diego F.)\|\|\|/items/f1fd12a7-edff-43c9-a8a8-425bd3a0d865 Andersen, J.B. (Jesper B.)\|\|\|/items/30522278-e252-4feb-9558-84b5c027103a Alvaro, D. (Domenico)\|\|\|/items/f9c14989-1042-4c59-a9b3-fd2c47c86939 Cardinale, V. (Vincenzo)\|\|\|/items/04ce3ed2-9b97-481b-87f3-b062ad49057d Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85 Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5 Aspichueta, P. (Patricia)\|\|\|/items/384763a9-5584-4c74-baec-92991a901d35
author	Ruiz-de-Gauna, M. (Mikel)\|\|\|/items/b3fdb2fe-141e-4e66-b98f-339736cf9274
author_facet	Ruiz-de-Gauna, M. (Mikel)\|\|\|/items/b3fdb2fe-141e-4e66-b98f-339736cf9274 Biancaniello, F. (Francesca)\|\|\|/items/d465cfda-d22e-46c9-9920-7558b1efb8b0 González-Romero, F. (Francisco)\|\|\|/items/27f57966-25e7-4089-9bb5-9cfcbc5747a2 Rodrigues, P.M. (Pedro M.)\|\|\|/items/b2eb48c0-8f5b-4ce3-8fa7-330864e4c609 Lapitz, A. (Ainhoa)\|\|\|/items/3ca2b075-145a-4acd-ae22-d52246e4778f Gómez-Santos, B. (Beatriz)\|\|\|/items/426fd680-44c0-4bb1-8f75-aec188bd070b Olaizola, P. (Paula)\|\|\|/items/5426b4b4-4ac7-46f7-8304-17cb549c08a4 Matteo, S. (Sabina) Di\|\|\|/items/067048b7-7419-4424-a836-e1d3acbd2c27 Aurrekoetxea, I. (Igor)\|\|\|/items/c109bf8d-7a3b-4b75-9cd6-05bc5e62331f Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66 Nieva-Zuluaga, A. (Ane)\|\|\|/items/5af56c2d-2f4c-4e29-8d04-4a95e9165960 Benito-Vicente, A. (Asier)\|\|\|/items/7827ee97-7b23-4456-a626-f950ea74fcc1 Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9 Apodaka-Biguri, M. (Maider)\|\|\|/items/14dbc28a-065f-40f6-9706-a34517e83351 Paiva, N.A. (Nuno A.)\|\|\|/items/8df71801-9888-4874-bdf6-6c956af0b3a0 Saenz-De-Urturi, D. (Diego)\|\|\|/items/9cae7551-eaae-49fd-a0f2-ee63e52246e5 Buque, X. (Xabier)\|\|\|/items/dac3924e-8d31-4515-9e76-f46cc41c0acc Delgado, I. (Igotz)\|\|\|/items/2fa21136-56fe-424e-81a8-67c78ab6b648 Martín, C. (Cesar)\|\|\|/items/86a97a3c-cf22-4c98-b915-e085b2cfeb92 Azkargorta, M. (Mikel)\|\|\|/items/3411ce9e-9088-4b6c-b9f2-4b055b8ef982 Elortza, F. (Felix)\|\|\|/items/b59cc8e8-12c0-448a-91fc-ef330149f608 Calvisi, D.F. (Diego F.)\|\|\|/items/f1fd12a7-edff-43c9-a8a8-425bd3a0d865 Andersen, J.B. (Jesper B.)\|\|\|/items/30522278-e252-4feb-9558-84b5c027103a Alvaro, D. (Domenico)\|\|\|/items/f9c14989-1042-4c59-a9b3-fd2c47c86939 Cardinale, V. (Vincenzo)\|\|\|/items/04ce3ed2-9b97-481b-87f3-b062ad49057d Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85 Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5 Aspichueta, P. (Patricia)\|\|\|/items/384763a9-5584-4c74-baec-92991a901d35
author_role	author
author2	Biancaniello, F. (Francesca)\|\|\|/items/d465cfda-d22e-46c9-9920-7558b1efb8b0 González-Romero, F. (Francisco)\|\|\|/items/27f57966-25e7-4089-9bb5-9cfcbc5747a2 Rodrigues, P.M. (Pedro M.)\|\|\|/items/b2eb48c0-8f5b-4ce3-8fa7-330864e4c609 Lapitz, A. (Ainhoa)\|\|\|/items/3ca2b075-145a-4acd-ae22-d52246e4778f Gómez-Santos, B. (Beatriz)\|\|\|/items/426fd680-44c0-4bb1-8f75-aec188bd070b Olaizola, P. (Paula)\|\|\|/items/5426b4b4-4ac7-46f7-8304-17cb549c08a4 Matteo, S. (Sabina) Di\|\|\|/items/067048b7-7419-4424-a836-e1d3acbd2c27 Aurrekoetxea, I. (Igor)\|\|\|/items/c109bf8d-7a3b-4b75-9cd6-05bc5e62331f Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66 Nieva-Zuluaga, A. (Ane)\|\|\|/items/5af56c2d-2f4c-4e29-8d04-4a95e9165960 Benito-Vicente, A. (Asier)\|\|\|/items/7827ee97-7b23-4456-a626-f950ea74fcc1 Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9 Apodaka-Biguri, M. (Maider)\|\|\|/items/14dbc28a-065f-40f6-9706-a34517e83351 Paiva, N.A. (Nuno A.)\|\|\|/items/8df71801-9888-4874-bdf6-6c956af0b3a0 Saenz-De-Urturi, D. (Diego)\|\|\|/items/9cae7551-eaae-49fd-a0f2-ee63e52246e5 Buque, X. (Xabier)\|\|\|/items/dac3924e-8d31-4515-9e76-f46cc41c0acc Delgado, I. (Igotz)\|\|\|/items/2fa21136-56fe-424e-81a8-67c78ab6b648 Martín, C. (Cesar)\|\|\|/items/86a97a3c-cf22-4c98-b915-e085b2cfeb92 Azkargorta, M. (Mikel)\|\|\|/items/3411ce9e-9088-4b6c-b9f2-4b055b8ef982 Elortza, F. (Felix)\|\|\|/items/b59cc8e8-12c0-448a-91fc-ef330149f608 Calvisi, D.F. (Diego F.)\|\|\|/items/f1fd12a7-edff-43c9-a8a8-425bd3a0d865 Andersen, J.B. (Jesper B.)\|\|\|/items/30522278-e252-4feb-9558-84b5c027103a Alvaro, D. (Domenico)\|\|\|/items/f9c14989-1042-4c59-a9b3-fd2c47c86939 Cardinale, V. (Vincenzo)\|\|\|/items/04ce3ed2-9b97-481b-87f3-b062ad49057d Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85 Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5 Aspichueta, P. (Patricia)\|\|\|/items/384763a9-5584-4c74-baec-92991a901d35
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv	Cholangiocarcinoma Biliary cancers Dismal prognosis Lipid metabolism
topic	Cholangiocarcinoma Biliary cancers Dismal prognosis Lipid metabolism
description	Background and aims: Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with a dismal prognosis. We investigated if lipid metabolism is disrupted in CCA and its role in tumor proliferation. Approach and results: The in vitro and in vivo tumorigenic capacity of five human CCA cell lines was analyzed. Proteome, lipid content, and metabolic fluxes were evaluated in CCA cells and compared with normal human cholangiocytes (NHC). The Akt1/NOTCH1 intracellular cytoplasmic domain (Nicd1)-driven CCA mouse model was also evaluated. The proteome of CCA cells was enriched in pathways involved in lipid and lipoprotein metabolism. The EGI1 CCA cell line presented the highest tumorigenic capacity. Metabolic studies in high (EGI1) versus low (HUCCT1) proliferative CCA cells in vitro showed that both EGI1 and HUCCT1 incorporated more fatty acids (FA) than NHC, leading to increased triglyceride storage, also observed in Akt1/Nicd1-driven CCA mouse model. The highly proliferative EGI1 CCA cells showed greater uptake of very-low-density and HDLs than NHC and HUCCT1 CCA cells and increased cholesteryl ester content. The FA oxidation (FAO) and related proteome enrichment were specifically up-regulated in EGI1, and consequently, pharmacological blockade of FAO induced more pronounced inhibition of their tumorigenic capacity compared with HUCCT1. The expression of acyl-CoA dehydrogenase ACADM, the first enzyme involved in FAO, was increased in human CCA tissues and correlated with the proliferation marker PCNA. Conclusions: Highly proliferative human CCA cells rely on lipid and lipoprotein uptake to fuel FA catabolism, suggesting that inhibition of FAO and/or lipid uptake could represent a therapeutic strategy for this CCA subclass.
publishDate	2022
dc.date.none.fl_str_mv	2022 2022-01-01 2022 2022-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10171/119012
url	https://hdl.handle.net/10171/119012
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
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.publisher.none.fl_str_mv	Wolters Kluwer Health
publisher.none.fl_str_mv	Wolters Kluwer Health
dc.source.none.fl_str_mv	reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str	Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str	Dadun. Depósito Académico Digital de la Universidad de Navarra
collection	Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869419440007806976
spelling	Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipidsRuiz-de-Gauna, M. (Mikel)\|\|\|/items/b3fdb2fe-141e-4e66-b98f-339736cf9274Biancaniello, F. (Francesca)\|\|\|/items/d465cfda-d22e-46c9-9920-7558b1efb8b0González-Romero, F. (Francisco)\|\|\|/items/27f57966-25e7-4089-9bb5-9cfcbc5747a2Rodrigues, P.M. (Pedro M.)\|\|\|/items/b2eb48c0-8f5b-4ce3-8fa7-330864e4c609Lapitz, A. (Ainhoa)\|\|\|/items/3ca2b075-145a-4acd-ae22-d52246e4778fGómez-Santos, B. (Beatriz)\|\|\|/items/426fd680-44c0-4bb1-8f75-aec188bd070bOlaizola, P. (Paula)\|\|\|/items/5426b4b4-4ac7-46f7-8304-17cb549c08a4Matteo, S. (Sabina) Di\|\|\|/items/067048b7-7419-4424-a836-e1d3acbd2c27Aurrekoetxea, I. (Igor)\|\|\|/items/c109bf8d-7a3b-4b75-9cd6-05bc5e62331fLabiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66Nieva-Zuluaga, A. (Ane)\|\|\|/items/5af56c2d-2f4c-4e29-8d04-4a95e9165960Benito-Vicente, A. (Asier)\|\|\|/items/7827ee97-7b23-4456-a626-f950ea74fcc1Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9Apodaka-Biguri, M. (Maider)\|\|\|/items/14dbc28a-065f-40f6-9706-a34517e83351Paiva, N.A. (Nuno A.)\|\|\|/items/8df71801-9888-4874-bdf6-6c956af0b3a0Saenz-De-Urturi, D. (Diego)\|\|\|/items/9cae7551-eaae-49fd-a0f2-ee63e52246e5Buque, X. (Xabier)\|\|\|/items/dac3924e-8d31-4515-9e76-f46cc41c0accDelgado, I. (Igotz)\|\|\|/items/2fa21136-56fe-424e-81a8-67c78ab6b648Martín, C. (Cesar)\|\|\|/items/86a97a3c-cf22-4c98-b915-e085b2cfeb92Azkargorta, M. (Mikel)\|\|\|/items/3411ce9e-9088-4b6c-b9f2-4b055b8ef982Elortza, F. (Felix)\|\|\|/items/b59cc8e8-12c0-448a-91fc-ef330149f608Calvisi, D.F. (Diego F.)\|\|\|/items/f1fd12a7-edff-43c9-a8a8-425bd3a0d865Andersen, J.B. (Jesper B.)\|\|\|/items/30522278-e252-4feb-9558-84b5c027103aAlvaro, D. (Domenico)\|\|\|/items/f9c14989-1042-4c59-a9b3-fd2c47c86939Cardinale, V. (Vincenzo)\|\|\|/items/04ce3ed2-9b97-481b-87f3-b062ad49057dBujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5Aspichueta, P. (Patricia)\|\|\|/items/384763a9-5584-4c74-baec-92991a901d35CholangiocarcinomaBiliary cancersDismal prognosisLipid metabolismBackground and aims: Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with a dismal prognosis. We investigated if lipid metabolism is disrupted in CCA and its role in tumor proliferation. Approach and results: The in vitro and in vivo tumorigenic capacity of five human CCA cell lines was analyzed. Proteome, lipid content, and metabolic fluxes were evaluated in CCA cells and compared with normal human cholangiocytes (NHC). The Akt1/NOTCH1 intracellular cytoplasmic domain (Nicd1)-driven CCA mouse model was also evaluated. The proteome of CCA cells was enriched in pathways involved in lipid and lipoprotein metabolism. The EGI1 CCA cell line presented the highest tumorigenic capacity. Metabolic studies in high (EGI1) versus low (HUCCT1) proliferative CCA cells in vitro showed that both EGI1 and HUCCT1 incorporated more fatty acids (FA) than NHC, leading to increased triglyceride storage, also observed in Akt1/Nicd1-driven CCA mouse model. The highly proliferative EGI1 CCA cells showed greater uptake of very-low-density and HDLs than NHC and HUCCT1 CCA cells and increased cholesteryl ester content. The FA oxidation (FAO) and related proteome enrichment were specifically up-regulated in EGI1, and consequently, pharmacological blockade of FAO induced more pronounced inhibition of their tumorigenic capacity compared with HUCCT1. The expression of acyl-CoA dehydrogenase ACADM, the first enzyme involved in FAO, was increased in human CCA tissues and correlated with the proliferation marker PCNA. Conclusions: Highly proliferative human CCA cells rely on lipid and lipoprotein uptake to fuel FA catabolism, suggesting that inhibition of FAO and/or lipid uptake could represent a therapeutic strategy for this CCA subclass.Wolters Kluwer HealthDadun. Depósito Académico Digital Universidad de Navarra20222022-01-0120222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/119012reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1190122026-06-21T12:47:57Z
score	15.812429

Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids

Similares en LA Referencia