CAIX forms a transport metabolon with monocarboxylate transporters in human breast cancer cells.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
12
06
2019
accepted:
04
11
2019
revised:
28
10
2019
pubmed:
15
11
2019
medline:
25
11
2020
entrez:
15
11
2019
Statut:
ppublish
Résumé
Tumor cells rely on glycolysis to meet their elevated demand for energy. Thereby they produce significant amounts of lactate and protons, which are exported via monocarboxylate transporters (MCTs), supporting the formation of an acidic microenvironment. The present study demonstrates that carbonic anhydrase IX (CAIX), one of the major acid/base regulators in cancer cells, forms a protein complex with MCT1 and MCT4 in tissue samples from human breast cancer patients, but not healthy breast tissue. Formation of this transport metabolon requires binding of CAIX to the Ig1 domain of the MCT1/4 chaperon CD147 and is required for CAIX-mediated facilitation of MCT1/4 activity. Application of an antibody, directed against the CD147-Ig1 domain, displaces CAIX from the transporter and suppresses CAIX-mediated facilitation of proton-coupled lactate transport. In cancer cells, this "metabolon disruption" results in a decrease in lactate transport, reduced glycolysis, and ultimately reduced cell proliferation. Taken together, the study shows that carbonic anhydrases form transport metabolons with acid/base transporters in human tumor tissue and that these interactions can be exploited to interfere with tumor metabolism and proliferation.
Identifiants
pubmed: 31723238
doi: 10.1038/s41388-019-1098-6
pii: 10.1038/s41388-019-1098-6
doi:
Substances chimiques
Monocarboxylic Acid Transporters
0
Muscle Proteins
0
SLC16A4 protein, human
0
Symporters
0
monocarboxylate transport protein 1
0
Basigin
136894-56-9
Carbonic Anhydrase IX
EC 4.2.1.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1710-1723Références
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