Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/32456
Registo completo
Campo DC | Valor | Idioma |
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dc.contributor.author | Granja, Sara Costa | por |
dc.contributor.author | Marchiq, Ibtissam | por |
dc.contributor.author | Le Floch, Renaud | por |
dc.contributor.author | Moura, Conceição Souto | por |
dc.contributor.author | Baltazar, Fátima | por |
dc.contributor.author | Pouysségur, Jacques | por |
dc.date.accessioned | 2015-01-07T12:37:10Z | - |
dc.date.available | 2015-01-07T12:37:10Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Granja, S., Marchiq, I., Le Floch, R., Moura, C. S., Baltazar, F., & Pouyssegur, J. (2015). Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status. Oncotarget, 6(9), 6708-6721. | - |
dc.identifier.issn | 1949-2553 | por |
dc.identifier.uri | https://hdl.handle.net/1822/32456 | - |
dc.description.abstract | Most cancers rely on aerobic glycolysis to generate energy and metabolic intermediates. To maintain a high glycolytic rate, cells must efficiently export lactic acid through the proton-coupled monocarboxylate transporters (MCT1/4). These transporters require a chaperone, CD147/BASIGIN (BSG) for trafficking to the plasma membrane and function. To validate the key role of these transporters in lung cancer, we first analysed the expression of MCT1/4 and BSG in 50 non-small lung cancer (NSCLC) cases. These proteins were specifically upregulated in tumour tissues. We then disrupted BSG in three NSCLC cell lines (A549, H1975 and H292) via ‘Zinc-Finger Nucleases’. The three homozygous BSG-/- cell lines displayed a low MCT activity (10- to 5-fold reduction, for MCT1 and MCT4, respectively) compared to wild-type cells. Consequently, the rate of glycolysis, compared to the wild-type counterpart, was reduced by 2.0- to 3.5-fold, whereas the rate of respiration was stimulated in BSG-/- cell lines. Both wild-type and BSG-null cells were extremely sensitive to the mitochondria inhibitor metformin/ phenformin in normoxia. However, only BSG-null cells, independently of their LKB1 status, remained sensitive to biguanides in hypoxia in vitro and tumour growth in nude mice. Our results demonstrate that inhibiting glycolysis by targeting lactic acid export sensitizes NSCLC to phenformin. | por |
dc.description.sponsorship | The JP team was funded from Ligue Nationale Contre le Cancer (LNCC Equipe labellisee), Fondation ARC, INCa, ANR, the EU-FP7 "METOXIA", SERVIER-CNRS, and Centre Lacassagne. SG received a fellowship from Fundacao para a Ciencia e Tecnologia (SFRH/BD/33503/2010) and IM was supported by a fellowship from LNCC. We thank Dr Susan Critchlow (AstraZeneca) for providing the iMCT1/2, the cytometry core facility (CYTOMED) for FACS analysis, and Dr. Christiane Brahimi-Horn for editorial correction of the manuscript. | por |
dc.language.iso | eng | por |
dc.publisher | Impact Journals | por |
dc.rights | openAccess | por |
dc.subject | Lung cancer | por |
dc.subject | CD147 | por |
dc.subject | BASIGIN | por |
dc.subject | Monocarboxylate transporters | por |
dc.subject | MCTs | por |
dc.subject | Lactate | por |
dc.subject | Glycolytic metabolism | por |
dc.subject | Metformin | por |
dc.subject | ZFNs | por |
dc.title | Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status | por |
dc.type | article | - |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=2862 | por |
sdum.publicationstatus | published | por |
oaire.citationStartPage | 6708 | por |
oaire.citationEndPage | 6721 | por |
oaire.citationIssue | 9 | por |
oaire.citationTitle | Oncotarget, Advance Publications | por |
oaire.citationVolume | 6 | por |
dc.date.updated | 2014-12-22T11:18:09Z | - |
dc.identifier.doi | 10.18632/oncotarget.2862 | por |
dc.identifier.pmid | 25894929 | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Oncotarget | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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granja s_oncotarget 2014.pdf | 2,36 MB | Adobe PDF | Ver/Abrir |