Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression

CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) av...

Full description

Bibliographic Details
Authors: Cano-Crespo, Sara, Chillarón Chaves, José Julio, Junza Martínez, Alexandra, Fernández-Miranda, Gonzalo, García Aymerich, Judith, Polte, Christine, Ballina, Laura R. de la, Ignatova, Zoya, Yanes, Oscar, Zorzano Olarte, Antonio, Stephan-Otto Attolini, Camille, Palacín Prieto, Manuel
Format: article
Status:Published version
Publication Date:2019
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/156737
Online Access:https://hdl.handle.net/2445/156737
Access Level:Open access
Keyword:Aminoàcids
Cèl·lules canceroses
Amino acids
Cancer cells
id ES_f45eec943f2f3cf821e63a78468f16ef
oai_identifier_str oai:diposit.ub.edu:2445/156737
network_acronym_str ES
network_name_str España
repository_id_str
spelling Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progressionCano-Crespo, SaraChillarón Chaves, José JulioJunza Martínez, AlexandraFernández-Miranda, GonzaloGarcía Aymerich, JudithPolte, ChristineBallina, Laura R. de laIgnatova, ZoyaYanes, OscarZorzano Olarte, AntonioStephan-Otto Attolini, CamillePalacín Prieto, ManuelAminoàcidsCèl·lules cancerosesAmino acidsCancer cellsCD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) availability while protecting cells from oxidative stress. Here we show that BCAA and AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis and cell proliferation caused by CD98hc ablation. Furthermore, our data indicate that CD98hc sustains glucose uptake and glycolysis, and, as a consequence, the pentose phosphate pathway (PPP). Thus, loss of CD98hc triggers a dramatic reduction in the nucleotide pool, which leads to replicative stress in these cells, as evidenced by the enhanced DNA Damage Response (DDR), S-phase delay and diminished rate of mitosis, all recovered by nucleoside supplementation. In addition, proper BCAA and AAA availability sustains the expression of the enzyme ribonucleotide reductase. In this regard, BCAA and AAA shortage results in decreased content of deoxynucleotides that triggers replicative stress, also recovered by nucleoside supplementation. On the basis of our findings, we conclude that CD98hc plays a central role in AA and glucose cellular nutrition, redox homeostasis and nucleotide availability, all key for cell proliferation.Nature Publishing Group2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/156737Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41598-019-50547-9Scientific Reports, 2019, vol. 9, p. 14065https://doi.org/10.1038/s41598-019-50547-9cc-by (c) Cano-Crespo, Sara et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1567372026-05-27T06:46:51Z
dc.title.none.fl_str_mv Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression
title Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression
spellingShingle Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression
Cano-Crespo, Sara
Aminoàcids
Cèl·lules canceroses
Amino acids
Cancer cells
title_short Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression
title_full Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression
title_fullStr Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression
title_full_unstemmed Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression
title_sort Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression
dc.creator.none.fl_str_mv Cano-Crespo, Sara
Chillarón Chaves, José Julio
Junza Martínez, Alexandra
Fernández-Miranda, Gonzalo
García Aymerich, Judith
Polte, Christine
Ballina, Laura R. de la
Ignatova, Zoya
Yanes, Oscar
Zorzano Olarte, Antonio
Stephan-Otto Attolini, Camille
Palacín Prieto, Manuel
author Cano-Crespo, Sara
author_facet Cano-Crespo, Sara
Chillarón Chaves, José Julio
Junza Martínez, Alexandra
Fernández-Miranda, Gonzalo
García Aymerich, Judith
Polte, Christine
Ballina, Laura R. de la
Ignatova, Zoya
Yanes, Oscar
Zorzano Olarte, Antonio
Stephan-Otto Attolini, Camille
Palacín Prieto, Manuel
author_role author
author2 Chillarón Chaves, José Julio
Junza Martínez, Alexandra
Fernández-Miranda, Gonzalo
García Aymerich, Judith
Polte, Christine
Ballina, Laura R. de la
Ignatova, Zoya
Yanes, Oscar
Zorzano Olarte, Antonio
Stephan-Otto Attolini, Camille
Palacín Prieto, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aminoàcids
Cèl·lules canceroses
Amino acids
Cancer cells
topic Aminoàcids
Cèl·lules canceroses
Amino acids
Cancer cells
description CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) availability while protecting cells from oxidative stress. Here we show that BCAA and AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis and cell proliferation caused by CD98hc ablation. Furthermore, our data indicate that CD98hc sustains glucose uptake and glycolysis, and, as a consequence, the pentose phosphate pathway (PPP). Thus, loss of CD98hc triggers a dramatic reduction in the nucleotide pool, which leads to replicative stress in these cells, as evidenced by the enhanced DNA Damage Response (DDR), S-phase delay and diminished rate of mitosis, all recovered by nucleoside supplementation. In addition, proper BCAA and AAA availability sustains the expression of the enzyme ribonucleotide reductase. In this regard, BCAA and AAA shortage results in decreased content of deoxynucleotides that triggers replicative stress, also recovered by nucleoside supplementation. On the basis of our findings, we conclude that CD98hc plays a central role in AA and glucose cellular nutrition, redox homeostasis and nucleotide availability, all key for cell proliferation.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/156737
url https://hdl.handle.net/2445/156737
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-019-50547-9
Scientific Reports, 2019, vol. 9, p. 14065
https://doi.org/10.1038/s41598-019-50547-9
dc.rights.none.fl_str_mv cc-by (c) Cano-Crespo, Sara et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Cano-Crespo, Sara et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869424465878712320
score 15.300719

Similar Items