The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Chronic acidosis in the tumour microenvironment selects for overexpression of LAMP2 in the plasma membrane
Open accessAbstract
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.
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Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327
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Acid-Mediated Tumor Invasion: a Multidisciplinary Study
Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B., & Gillies, R. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4193 · Cited by 771
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Vaupel, P., Schmidberger, H., & Mayer, A. (2019) · International Journal of Radiation Biology · doi:10.1080/09553002.2019.1589653 · Cited by 893
Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy
Pilon-Thomas, S., Kodumudi, K. N., El-Kenawi, A. E., Russell, S., Weber, A. M., Luddy, K., Damaghi, M., Wojtkowiak, J. W., Mulé, J. J., Ibrahim-Hashim, A., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-1743 · Cited by 593
Self-citationClassifying the evolutionary and ecological features of neoplasms
Maley, C. C., Aktipis, A., Graham, T. A., Sottoriva, A., Boddy, A. M., Janiszewska, M., Silva, A. S., Gerlinger, M., Yuan, Y., Pienta, K. J., et al. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.69 · Cited by 423
Self-citationTumor Microenvironment and Differential Responses to Therapy
Hirata, E., & Sahai, E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026781 · Cited by 422
Causes, consequences, and therapy of tumors acidosis
Pillai, S. R., Damaghi, M., Marunaka, Y., Spugnini, E. P., Fais, S., & Gillies, R. J. (2019) · Cancer and Metastasis Reviews · doi:10.1007/s10555-019-09792-7 · Cited by 282
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Metadata
- Authors
- Damaghi, M., Tafreshi, N. K., Lloyd, M. C., Sprung, R., Estrella, V., Wojtkowiak, J. W., Morse, D. L., Koomen, J. M., Bui, M. M., Gatenby, R. A., & Gillies, R. J.
- Venue
- Nature Communications
- Published
- 2015-12-10
- Volume
- 6
- Issue
- 1
- Pages
- 8752-8752
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2270643969
- Cited by
- 185
- References
- 4
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- gold
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- Damaghi, M., Tafreshi, N. K., Lloyd, M. C., Sprung, R., Estrella, V., Wojtkowiak, J. W., Morse, D. L., Koomen, J. M., Bui, M. M., Gatenby, R. A., & Gillies, R. J. (2015). Chronic acidosis in the tumour microenvironment selects for overexpression of LAMP2 in the plasma membrane. Nature Communications. https://doi.org/10.1038/ncomms9752
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