Chronic acidosis in the tumour microenvironment selects for overexpression of LAMP2 in the plasma membrane.
Nat Commun
; 6: 8752, 2015 Dec 10.
Article
en En
| MEDLINE
| ID: mdl-26658462
ABSTRACT
Early cancers are avascular and hence, profoundly acidic. Pre-malignant cells must adapt to acidosis to thrive in this hostile microenvironment. Here, we investigate MCF-7 cells that are adapted to grow in acidic conditions using SILAC proteomics and we reveal a significant upregulation of lysosomal proteins. Prominent among these is LAMP2 that functions to protect lysosomal membranes from acid proteolysis. LAMP2 upregulation by acidosis is confirmed both in vitro and in vivo. Furthermore, we show that the depletion of LAMP2 is sufficient to increase acidosis-mediated toxicity. In breast cancer patient samples, there is a high correlation of LAMP2 mRNA and protein expression with progression. We also observe that LAMP2 is located at the plasma membrane in clinical samples and this redistribution is acid-induced in vitro. Our findings suggest a potential adaptive mechanism, wherein cells chronically exposed to an acidic environment translocate lysosomal proteins to their surface, thus protecting the plasmalemma from acid-induced hydrolysis.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
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Membrana Celular
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Proteína 2 de la Membrana Asociada a los Lisosomas
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Neoplasias
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos