Deciphering the galectin-12 protein interactome reveals a major impact of galectin-12 on glutamine anaplerosis in colon cancer cells.
Exp Cell Res
; 379(2): 129-139, 2019 06 15.
Article
em En
| MEDLINE
| ID: mdl-30935948
ABSTRACT
Galectins are ß-galactoside binding proteins which possess a variety of functions including modulation of apoptosis, growth and differentiation. Hence, alterations in the expression profile have been associated with loss of cellular homeostasis contributing to tumor growth and progression. Though galectin-12 is significantly downregulated in several tumor entities, including colon cancer, its impact on cellular homeostasis as well as galectin-12 specific binding partners have not been identified so far. We therefore established an experimental strategy which is based on reversible cross-link immunoprecipitation to capture the galectin-12 protein interactome in colon cancer cells. By applying this approach, we identified 10 novel candidates of galectin-12 interacting proteins including the neutral amino acid exchanger SLC1A5. Remarkably, we uncovered that binding of galectin-12 to SLC1A5 significantly reduced glutamine uptake in our model cell line. Consequently, utilization of glutamine carbon for biomass synthesis was profoundly affected, suggesting galectin-12 as a novel inhibitor of glutamine anaplerosis in colon cancer cells. More detailed analysis revealed that colon cancer cells can counteract galectin-12 mediated glutamine deprivation by induction of compensatory mechanisms which facilitate adaption to low-glutamine conditions and thus survival.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Histocompatibilidade Menor
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Neoplasias do Colo
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Sistema ASC de Transporte de Aminoácidos
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Galectinas
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Glutamina
Limite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha