Chronic acidosis in the tumour microenvironment selects for overexpression of LAMP2 in the plasma membrane.

摘要: Early cancers are avascular and hence, profoundly acidic. Pre-malignant cells must adapt to acidosis thrive in this hostile microenvironment. Here, we investigate MCF-7 that adapted grow acidic conditions using SILAC proteomics reveal a significant upregulation of lysosomal proteins. Prominent among these is LAMP2 functions protect membranes from acid proteolysis. by confirmed both vitro vivo. Furthermore, show the depletion sufficient increase acidosis-mediated toxicity. In breast cancer patient samples, there high correlation mRNA protein expression with progression. We also observe located at plasma membrane clinical samples redistribution acid-induced vitro. Our findings suggest potential adaptive mechanism, wherein chronically exposed an environment translocate proteins their surface, thus protecting plasmalemma hydrolysis.