The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt‐based anti‐cancer drugs
Open accessAbstract
Although platinum-based drugs are widely used chemotherapeutics for cancer treatment, the determinants of tumor cell responsiveness remain poorly understood. We show that the loss of subunits LRRC8A and LRRC8D of the heteromeric LRRC8 volume-regulated anion channels (VRACs) increased resistance to clinically relevant cisplatin/carboplatin concentrations. Under isotonic conditions, about 50% of cisplatin uptake depended on LRRC8A and LRRC8D, but neither on LRRC8C nor on LRRC8E. Cell swelling strongly enhanced LRRC8-dependent cisplatin uptake, bolstering the notion that cisplatin enters cells through VRAC. LRRC8A disruption also suppressed drug-induced apoptosis independently from drug uptake, possibly by impairing VRAC-dependent apoptotic cell volume decrease. Hence, by mediating cisplatin uptake and facilitating apoptosis, VRAC plays a dual role in the cellular drug response. Incorporation of the LRRC8D subunit into VRAC substantially increased its permeability for cisplatin and the cellular osmolyte taurine, indicating that LRRC8 proteins form the channel pore. Our work suggests that LRRC8D-containing VRACs are crucial for cell volume regulation by an important organic osmolyte and may influence cisplatin/carboplatin responsiveness of tumors.
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Cites
The resurgence of platinum-based cancer chemotherapy
Kelland, L. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2167 · Cited by 4,717
Whole–genome characterization of chemoresistant ovarian cancer
Patch, A.-M., Christie, E. L., Etemadmoghadam, D., Garsed, D. W., George, J., Fereday, S., Nones, K., Cowin, P., Alsop, K., Bailey, P. J., et al. (2015) · Nature · doi:10.1038/nature14410 · Cited by 1,569
The role of apoptosis in cancer development and treatment response
Brown, J. M., & Attardi, L. D. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1560 · Cited by 944
Maeno, E., Ishizaki, Y., Kanaseki, T., Hazama, A., & Okada, Y. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.140216197 · Cited by 707
Okada, Y. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.273.3.c755 · Cited by 652
Voss, F. K., Ullrich, F., Münch, J., Lazarow, K., Lutter, D., Mah, N., Andrade-Navarro, M. A., von Kries, J. P., Stauber, T., & Jentsch, T. J. (2014) · Science · doi:10.1126/science.1252826 · Cited by 619
Self-citationCellular accumulation of the anticancer agent cisplatin: A review
Gately, D., & Howell, S. (1993) · British Journal of Cancer · doi:10.1038/bjc.1993.221 · Cited by 572
SWELL1, a Plasma Membrane Protein, Is an Essential Component of Volume-Regulated Anion Channel
Qiu, Z., Dubin, A. E., Mathur, J., Tu, B., Reddy, K., Miraglia, L. J., Reinhardt, J., Orth, A. P., & Patapoutian, A. (2014) · Cell · doi:10.1016/j.cell.2014.03.024 · Cited by 571
Cisplatin Induces Endoplasmic Reticulum Stress and Nucleus-independent Apoptotic Signaling
Mandic, A., Hansson, J., Linder, S., & Shoshan, M. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210284200 · Cited by 509
Haploid Genetic Screens in Human Cells Identify Host Factors Used by Pathogens
Carette, J. E., Guimaraes, C. P., Varadarajan, M., Park, A. S., Wuethrich, I., Godarova, A., Kotecki, M., Cochran, B. H., Spooner, E., Ploegh, H. L., et al. (2009) · Science · doi:10.1126/science.1178955 · Cited by 489
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Cited by
CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease
Jentsch, T. J., & Pusch, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00047.2017 · Cited by 448
Self-citationVRACs and other ion channels and transporters in the regulation of cell volume and beyond
Jentsch, T. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.29 · Cited by 353
Self-citationStover, E. H., Baco, M. B., Cohen, O., Li, Y. Y., Christie, E. L., Bagul, M., Goodale, A., Lee, Y., Pantel, S., Rees, M. G., et al. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-1243 · Cited by 49
“Other genes for which knockout was associated with response to individual drugs included spindle assembly checkpoint genes associated with paclitaxel response (33) and cisplatin importer LRRC8A associated with cisplatin resistance (34), confirming that the screen identified genes relevant to chemotherapy response.”
Background
Metadata
- Authors
- Planells‐Cases, R., Lutter, D., Guyader, C., Gerhards, N. M., Ullrich, F., Elger, D. A., Kucukosmanoglu, A., Xu, G., Voss, F. K., Reincke, S. M., Stauber, T., Blomen, V. A., Vis, D. J., Wessels, L. F., Brummelkamp, T. R., Borst, P., Rottenberg, S., & Jentsch, T. J.
- Venue
- The EMBO Journal
- Published
- 2015-11-03
- Volume
- 34
- Issue
- 24
- Pages
- 2993-3008
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- OpenAlex
- W2126297765
- Cited by
- 256
- References
- 51
- FWCI
- 9.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Planells‐Cases, R., Lutter, D., Guyader, C., Gerhards, N. M., Ullrich, F., Elger, D. A., Kucukosmanoglu, A., Xu, G., Voss, F. K., Reincke, S. M., Stauber, T., Blomen, V. A., Vis, D. J., Wessels, L. F., Brummelkamp, T. R., Borst, P., Rottenberg, S., & Jentsch, T. J. (2015). Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt‐based anti‐cancer drugs. The EMBO Journal. https://doi.org/10.15252/embj.201592409
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