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lamp, cells, cancer, expression, tumour, article, fig, tumours, acidic, google, scholar, breast, mcf, cell, cas, acidosis, acidadapted, acid, supplementary, membrane, samples, proteins, protein, lysosomal, normal, nature, growth, adaptation, min, analysis, data, size, ihc, positive, showed, spheroids, metastasis, staining, observed, acidity, glut, microenvironment, extracellular, knockdown, regions, conditions, proteomics, increased, dcis, areas,

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nature portfolio privacy policy human body index author information authors nature reviews advertising nature 0/ reprints middle national research council army medical research exhibit regional expression quantitative reverse transcription–pcr extreme acid-induced cytotoxicity mda-mb-231 clone d5 ms/ms mass tolerance human subjects protocol acid-activated lysosomal proteases discovered low-ph-induced proteins acid-sensitive caged compounds acid-induced cancer cell acid-mediated tumor invasion actionable information content acid-mediated tumor proteolysis ph-sensitive fluorescent dye acid-naive stromal cells range mass accuracies research institute silac-based quantitative proteomics acid-adapted cells induced tail-vain-injected snarf high aerobic glycolysis deadly disease-causing agents lc–ms/ms analysis false-positive biomarker association 40 mm tcep/100 mm dithiothreitol severe combined immune-deficiency permissions isoelectric focusing fractionation acid-induced behaviour observed reverse transcription–pcr c18 reversed-phase resin shrna-treated parental cells shotgun data set low ph-induced vegf acid-induced lysosomal proteins low-ph culture conditions access lc–ms/ms samples gene expression omnibus

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         headline:Chronic acidosis in the tumour microenvironment selects for overexpression of LAMP2 in the plasma membrane
         description: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. The protein LAMP2 functions to protect lysosomal membranes from acid proteolysis. In this study, the authors show that malignant cells adapt to the acidic tumour microenvironment by redirecting LAMP2 from lysosomes to the plasma membrane.
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      headline:Chronic acidosis in the tumour microenvironment selects for overexpression of LAMP2 in the plasma membrane
      description: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. The protein LAMP2 functions to protect lysosomal membranes from acid proteolysis. In this study, the authors show that malignant cells adapt to the acidic tumour microenvironment by redirecting LAMP2 from lysosomes to the plasma membrane.
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