ABCG2 transports anticancer drugs via a closed-to-open switch
Open accessAbstract
ABCG2 is an ABC transporter that extrudes a variety of compounds from cells, and presents an obstacle in treating chemotherapy-resistant cancers. Despite recent structural insights, no anticancer drug bound to ABCG2 has been resolved, and the mechanisms of multidrug transport remain obscure. Such a gap of knowledge limits the development of novel compounds that block or evade this critical molecular pump. Here we present single-particle cryo-EM studies of ABCG2 in the apo state, and bound to the three structurally distinct chemotherapeutics. Without the binding of conformation-selective antibody fragments or inhibitors, the resting ABCG2 adopts a closed conformation. Our cryo-EM, biochemical, and functional analyses reveal the binding mode of three chemotherapeutic compounds, demonstrate how these molecules open the closed conformation of the transporter, and establish that imatinib is particularly effective in stabilizing the inward facing conformation of ABCG2. Together these studies reveal the previously unrecognized conformational cycle of ABCG2.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ABCG2 plays an important role in ABC-dependent drug efflux, is capable of transporting chemotherapeutic agents such as paclitaxel and doxorubicin, and confers drug resistance leading to high recurrence and poor survival in hepatocellular carcinoma patients.
“Among them, ABCG2, one of the initially discovered transporters, plays an important role in the ABC-dependent drug efflux, and is capable of transporting a broad range of chemotherapeutic agents such as paclitaxel and doxorubicin (DOX), thus conferring the drug resistance and further leading to high recurrence and poor survival of patients bearing HCC.11–13”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · see citing works
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works
<i>PHENIX</i> : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716 · see citing works
Overview of the <i>CCP</i> 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353 · see citing works
MotionCor2 - anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S., Palovcak, E. J., Armache, J., Verba, K., Cheng, Y.-F., & Agard, D. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,678 · see citing works
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkòczi, G., Chen, V. B., Davis, I., Echols, N., Headd, J. J., Hung, L., Kapral, G. J., Grosse‐Kunstleve, R. W., et al. (2012) · International Tables for Crystallography · doi:10.1107/97809553602060000865 · Cited by 7,334 · see citing works
RELION: Implementation of a Bayesian approach to cryo-EM structure determination
Scheres, S. H. W. (2012) · Journal of Structural Biology · doi:10.1016/j.jsb.2012.09.006 · Cited by 5,446 · see citing works
CTFFIND4: Fast and accurate defocus estimation from electron micrographs
Rohou, A. L., & Grigorieff, N. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.08.008 · Cited by 4,926 · see citing works
Targeting multidrug resistance in cancer
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609 · see citing works
Revisiting the role of ABC transporters in multidrug-resistant cancer
Robey, R. W., Pluchino, K. M., Hall, M. D., Fojo, A. T., Bates, S. E., & Gottesman, M. M. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0005-8 · Cited by 1,866 · see citing works
Quantifying the local resolution of cryo-EM density maps
Kucukelbir, A., Sigworth, F. J., & Tagare, H. D. (2013) · Nature Methods · doi:10.1038/nmeth.2727 · Cited by 1,763 · see citing works
Allen, J. D., van Loevezijn, A., Rademaker-Lakhai, J. M., van der Valk, M., van Tellingen, O., Reid, G., Schellens, J. H. M., Koomen, G., & Schinkel, A. H. (2002) · PubMed · Cited by 690 · see citing works
Role of the Breast Cancer Resistance Protein (BCRP/ABCG2) in Drug Transport—an Update
Mao, Q., & Unadkat, J. D. (2014) · The AAPS Journal · doi:10.1208/s12248-014-9668-6 · Cited by 676 · see citing works
ABC Transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development
Choi, Y. H., & Yu, A. (2014) · Current Pharmaceutical Design · doi:10.2174/138161282005140214165212 · Cited by 633 · see citing works
Overview of the CCP4 suite and current developments.
Winn, M. D., Ballard, C. C., Cowtan, K. D., et al. (2011) · Apollo (University of Cambridge) · doi:10.17863/cam.52322 · Cited by 564 · see citing works
Sampling the conformational space of the catalytic subunit of human γ-secretase
Bai, X., Rajendra, E., Yang, G., Shi, Y., & Scheres, S. H. W. (2015) · eLife · doi:10.7554/elife.11182 · Cited by 554 · see citing works
Software tools for automated transmission electron microscopy
Schorb, M., Haberbosch, I., Hagen, W. J. H., Schwab, Y., & Mastronarde, D. N. (2019) · Nature Methods · doi:10.1038/s41592-019-0396-9 · Cited by 508 · see citing works
Imatinib: A Breakthrough of Targeted Therapy in Cancer
Iqbal, N., & Iqbal, N. (2014) · Chemotherapy Research and Practice · doi:10.1155/2014/357027 · Cited by 481 · see citing works
JLigand: a graphical tool for the CCP4 template-restraint library
Lebedev, A. A., Young, P., Isupov, M. N., Moroz, O. V., Vagin, A. A., & Murshudov, G. N. (2012) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744491200251x · Cited by 439 · see citing works
Honjo, Y., Hrycyna, C. A., Yan, Q. W., Medina-Pérez, W. Y., Robey, R. W., van de Laar, A., Litman, T., Dean, M. C., & Bates, S. E. (2001) · PubMed · Cited by 429 · see citing works
Structural insight into substrate and inhibitor discrimination by human P-glycoprotein
Alam, A., Kowal, J., Broude, E., Roninson, I., & Locher, K. (2019) · Science · doi:10.1126/science.aav7102 · Cited by 426 · see citing works
Burger, H., van Tol, H., Boersma, A. W. M., Brok, M. O., Wiemer, E. A. C., Stoter, G., & Nooter, K. (2004) · Blood · doi:10.1182/blood-2004-04-1398 · Cited by 418 · see citing works
Structure of the human multidrug transporter ABCG2
Taylor, N. M. I., Manolaridis, I., Jackson, S. M., Kowal, J., Stahlberg, H., & Locher, K. P. (2017) · Nature · doi:10.1038/nature22345 · Cited by 418 · see citing works
Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1
Johnson, Z. L., & Chen, J. (2017) · Cell · doi:10.1016/j.cell.2017.01.041 · Cited by 375 · see citing works
Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity
Robey, R. W., Honjo, Y., Morisaki, K., Nadjem, T., Runge, S., Risbood, M., Poruchynsky, M. S., & Bates, S. E. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601370 · Cited by 367 · see citing works
Structural basis of small-molecule inhibition of human multidrug transporter ABCG2
Jackson, S. M., Manolaridis, I., Kowal, J., Zechner, M., Taylor, N. M. I., Bause, M., Bauer, S., Bartholomäus, R., Bernhardt, G., König, B., et al. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0049-1 · Cited by 325 · see citing works
Houghton, P. J., Germain, G. S., Harwood, F. C., Schuetz, J. D., Stewart, C. F., Buchdunger, E., & Traxler, P. M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3344 · Cited by 323 · see citing works
Likelihood-based classification of cryo-EM images using FREALIGN
Lyumkis, D., Brilot, A., Theobald, D., & Grigorieff, N. (2013) · Journal of Structural Biology · doi:10.1016/j.jsb.2013.07.005 · Cited by 290 · see citing works
Structural basis of MsbA-mediated lipopolysaccharide transport
Mi, W., Li, Y., Yoon, S. H., Ernst, R. K., Walz, T., & Liao, M. (2017) · Nature · doi:10.1038/nature23649 · Cited by 260 · see citing works
Self-citationCryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and substrate-bound states
Manolaridis, I., Jackson, S. M., Taylor, N. M. I., Kowal, J., Stahlberg, H., & Locher, K. P. (2018) · Nature · doi:10.1038/s41586-018-0680-3 · Cited by 228 · see citing works
Human ABCG2: structure, function, and its role in multidrug resistance.
Mo, W., & Zhang, J. (2012) · PubMed Central · Cited by 218 · see citing works
Expression and functional characterization of ABCG2 in brain endothelial cells and vessels
Zhang, W., Mojsilovic‐Petrovic, J., Andrade, M. F., Zhang, H., Ball, M., & Stanimirovic, D. B. (2003) · The FASEB Journal · doi:10.1096/fj.02-1131fje · Cited by 204 · see citing works
Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures
Ru, H., Chambers, M. G., Fu, T., Tong, A., Liao, M., & Wu, H. (2015) · Cell · doi:10.1016/j.cell.2015.10.055 · Cited by 191 · see citing works
Self-citationABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan‐treated metastases
Candeil, L., Gourdier, I., Peyron, D., Vezzio, N., Copois, V., Bibeau, F., Orsetti, B., Scheffer, G. L., Ychou, M., Khan, Q. A., et al. (2004) · International Journal of Cancer · doi:10.1002/ijc.20032 · Cited by 180 · see citing works
Gutmann, H., Hruz, P. L., Zimmermann, C., Beglinger, C., & Drewe, J. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.05.031 · Cited by 171 · see citing works
Structural basis of lipopolysaccharide extraction by the LptB2FGC complex
Li, Y., Orlando, B. J., & Liao, M. (2019) · Nature · doi:10.1038/s41586-019-1025-6 · Cited by 166 · see citing works
Self-citationInhibitors of Human ABCG2: From Technical Background to Recent Updates With Clinical Implications
Toyoda, Y., Takada, T., & Suzuki, H. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00208 · Cited by 155 · see citing works
Cryo-EM structure of the ABCG2 E211Q mutant bound to estrone 3-sulfate and 5D3-Fab
Manolaridis, I., Jackson, S. M., Taylor, N. M. I., Kowal, J., Stahlberg, H., & Locher, K. P. (2018) · Worldwide Protein Data Bank · doi:10.2210/pdb6hco/pdb · Cited by 144 · see citing works
Henriksen, U., Fog, J. U., Litman, T., & Gether, U. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502937200 · Cited by 119 · see citing works
Multiple drugbinding sites on the R482G isoform of the ABCG2 transporter
Clark, R., Kerr, I. D., & Callaghan, R. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706904 · Cited by 108 · see citing works
Shukla, S., Robey, R. W., Bates, S. E., & Ambudkar, S. V. (2006) · Biochemistry · doi:10.1021/bi060552f · Cited by 103 · see citing works
Özvegy‐Laczka, C., Várady, G., Köblös, G., Ujhelly, O., Cervenak, J., Schuetz, J. D., Sorrentino, B. P., Koomen, G., Váradi, A., Német, K., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411338200 · Cited by 92 · see citing works
Interaction of the Efflux Transporters ABCB1 and ABCG2 With Imatinib, Nilotinib, and Dasatinib
Eadie, L. N., Hughes, T. P., & White, D. L. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2013.208 · Cited by 89 · see citing works
Bryostatin-I—An Antineoplastic Treasure from the Deep?
May, W. S., & Ruvolo, P. P. (2002) · Cancer Biology & Therapy · doi:10.4161/cbt.1.4.20 · Cited by 88 · see citing works
Giri, N., Agarwal, S., Shaik, N. M., Pan, G., Chen, Y., & Elmquist, W. F. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.022046 · Cited by 85 · see citing works
Özvegy‐Laczka, C., Köblös, G., Sarkadi, B., & Váradi, A. (2004) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2004.11.005 · Cited by 80 · see citing works
The structure of the human ABC transporter ABCG2 reveals a novel mechanism for drug extrusion
Khunweeraphong, N., Stockner, T., & Kuchler, K. (2017) · Scientific Reports · doi:10.1038/s41598-017-11794-w · Cited by 77 · see citing works
Ejendal, K. F. K., Diop, N. K., Schweiger, L. C., & Hrycyna, C. A. (2006) · Protein Science · doi:10.1110/ps.051998406 · Cited by 69 · see citing works
Human Multidrug Transporter ABCG2, a Target for Sensitizing Drug Resistance in Cancer Chemotherapy
Xu, J., Peng, H., & Zhang, J. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707780059580 · Cited by 51 · see citing works
Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2?
McDevitt, C. A., Crowley, E. H., Hobbs, G., Starr, K. J., Kerr, I. D., & Callaghan, R. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06578.x · Cited by 46 · see citing works
Telbisz, Á., Hegedüs, C., Özvegy‐Laczka, C., Goda, K., Várady, G., Takáts, Z., Szabó, E., Sorrentino, B. P., Váradi, A., & Sarkadi, B. (2011) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2011.10.021 · Cited by 41 · see citing works
Mitoxantrone is expelled by the ABCG2 multidrug transporter directly from the plasma membrane
Homolya, L., Orbán, T. I., Csanády, L., & Sarkadi, B. (2010) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2010.07.031 · Cited by 40 · see citing works
Iorio, A. L., Ros, M. D., Fantappiè, O., Lucchesi, M., Facchini, L., Stival, A., Becciani, S., Guidi, M., Favre, C., de Martino, M., et al. (2016) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520616666151120121928 · Cited by 40 · see citing works
Ni, Z., Bikádi, Z., Shuster, D. L., Zhao, C., Rosenberg, M. F., & Mao, Q. (2011) · Biochemistry · doi:10.1021/bi200573t · Cited by 33 · see citing works
Cai, X., Bikádi, Z., Ni, Z., Lee, E., Wang, H., Rosenberg, M. F., & Mao, Q. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.163493 · Cited by 32 · see citing works
Haider, A. J., Cox, M. H., Jones, N., Goode, A., Bridge, K. S., Wong, K., Briggs, D. A., & Kerr, I. D. (2015) · Bioscience Reports · doi:10.1042/bsr20150150 · Cited by 31 · see citing works
Residues contributing to drug transport by ABCG2 are localised to multiple drug-binding pockets
Cox, M. H., Kapoor, P., Briggs, D. A., & Kerr, I. D. (2018) · Biochemical Journal · doi:10.1042/bcj20170923 · Cited by 25 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Software tools for automated transmission electron microscopy
Schorb, M., Haberbosch, I., Hagen, W. J. H., Schwab, Y., & Mastronarde, D. N. (2019) · Nature Methods · doi:10.1038/s41592-019-0396-9 · Cited by 508 · see citing works
Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming
Mattioli, R., Ilari, A., Colotti, B., Mosca, L., Fazi, F., & Colotti, G. (2023) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2023.101205 · Cited by 303 · see citing works
Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance
Xiao, H., Zheng, Y., Ma, L., Tian, L., & Sun, Q. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.648407 · Cited by 264 · see citing works
Membrane transporters in drug development and as determinants of precision medicine
Galetin, A., Brouwer, K. L. R., Tweedie, D., Yoshida, K. J., Sjöstedt, N., Aleksunes, L. M., Chu, X., Evers, R., Hafey, M. J., Lai, Y., et al. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00877-1 · Cited by 246 · see citing works
Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters
Sajid, A., Rahman, H., & Ambudkar, S. V. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00612-3 · Cited by 216 · see citing works
Structure and Mechanism of Human ABC Transporters
Alam, A., & Locher, K. P. (2023) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-111622-091232 · Cited by 200 · see citing works
Fan, J., To, K. K. W., Chen, Z., & Fu, L. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100905 · Cited by 185 · see citing works
ATP-binding cassette efflux transporters and MDR in cancer
Pote, M. S., & Gacche, R. N. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103537 · Cited by 162 · see citing works
Wang, Y., Wang, Y., Qin, Z., Cai, S., Yu, L., Hu, H., & Zeng, S. (2021) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2021.1887139 · Cited by 140 · see citing works
The potential of probiotics in the amelioration of hyperuricemia
Zhao, H., Lu, Z., & Lu, Y. (2022) · Food & Function · doi:10.1039/d1fo03206b · Cited by 128 · see citing works
Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5
Harris, A., Wagner, M., Du, D., Raschka, S. L., Nentwig, L., Gohlke, H., Smits, S. H. J., Luisi, B. F., & Schmitt, L. (2021) · Nature Communications · doi:10.1038/s41467-021-25574-8 · Cited by 114 · see citing works
Zhao, H., Chen, X., Zhang, L., Meng, F., Zhou, L., Pang, X., Lu, Z., & Lu, Y. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106350 · Cited by 106 · see citing works
Chen, J., Jiang, Z., Xu, W., Sun, T., Zhuang, X., Ding, J., & Chen, X. (2020) · Nano Letters · doi:10.1021/acs.nanolett.0c02515 · Cited by 102 · see citing works
VARIDT 2.0: structural variability of drug transporter
Fu, T., Li, F., Zhang, Y., Yin, J., Qiu, W., Li, X., Liu, X., Xin, W., Wang, C., Yu, L., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1013 · Cited by 88 · see citing works
Zattoni, I. F., Delabio, L. C., Dutra, J. D. P., Kita, D. H., Scheiffer, G., Hembecker, M., Pereira, G. D. S., Moure, V. R., & Valdameri, G. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114346 · Cited by 88 · see citing works
Structural Basis of Drug Recognition by the Multidrug Transporter ABCG2
Kowal, J., Ni, D., Jackson, S. M., Manolaridis, I., Stahlberg, H., & Locher, K. P. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.166980 · Cited by 82 · see citing works
Highlighting membrane protein structure and function: A celebration of the Protein Data Bank
Li, F., Egea, P. F., Vecchio, A. J., Asial, I., Gupta, M., Paulino, J., Bajaj, R., Dickinson, M. S., Ferguson-Miller, S. M., Monk, B. C., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100557 · Cited by 81 · see citing works
Structures of ABCG2 under turnover conditions reveal a key step in the drug transport mechanism
Yu, Q., Ni, D., Kowal, J., Manolaridis, I., Jackson, S. M., Stahlberg, H., & Locher, K. P. (2021) · Nature Communications · doi:10.1038/s41467-021-24651-2 · Cited by 80 · see citing works
Gonçalves, B. M. F., Cardoso, D., & Ferreira, M. U. (2020) · Molecules · doi:10.3390/molecules25153364 · Cited by 74 · see citing works
Structure and Function of Hepatobiliary ATP Binding Cassette Transporters
Kroll, T., Prescher, M., Smits, S. H. J., & Schmitt, L. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00659 · Cited by 73 · see citing works
Wang, X., Wang, L., Wei, X., Xu, C., Cavender, G. A., Walker, L. L., & Sun, S. (2024) · Journal of Dairy Science · doi:10.3168/jds.2024-25322 · Cited by 83 · see citing works
Goebel, J., Chmielewski, J. A., & Hrycyna, C. A. (2021) · Cancer Drug Resistance · doi:10.20517/cdr.2021.19 · Cited by 70 · see citing works
The ABCG2/BCRP transporter and its variants – from structure to pathology
Sarkadi, B., Homolya, L., & Hegedűs, T. (2020) · FEBS Letters · doi:10.1002/1873-3468.13947 · Cited by 61 · see citing works
Khunweeraphong, N., & Kuchler, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094806 · Cited by 54 · see citing works
Distinct allosteric mechanisms of first-generation MsbA inhibitors
Thélot, F. A., Zhang, W., Song, K., Xu, C., Huang, J., & Liao, M. (2021) · Science · doi:10.1126/science.abi9009 · Cited by 48 · see citing works
Self-citationPerspectives on drug repurposing to overcome cancer multidrug resistance mediated by ABCB1 and ABCG2
Wu, C., Hsiao, S.-H., & Wu, Y. (2023) · Drug Resistance Updates · doi:10.1016/j.drup.2023.101011 · Cited by 47 · see citing works
Squeeze pumping of lipids and insecticides by ABCH transporter
Chen, J., Duan, Y., Zhou, Y., & Yang, Q. (2024) · Cell · doi:10.1016/j.cell.2024.11.033 · Cited by 45 · see citing works
Shi, X., Deng, Y., Liu, X., Gao, G., Wang, R., & Liang, G. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2022.114212 · Cited by 44 · see citing works
Liang, X., Wang, Y., Shi, H., Dong, M., Han, H., & Li, Q. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s304526 · Cited by 41 · see citing works
Structural basis for abscisic acid efflux mediated by ABCG25 in Arabidopsis thaliana
Wei, Y. J., Liao, L., Wei, H., Gao, Y., Liu, X., & Sun, L. (2023) · Nature Plants · doi:10.1038/s41477-023-01510-0 · Cited by 42 · see citing works
Rasouli, A., Yu, Q., Dehghani‐Ghahnaviyeh, S., Wen, P., Kowal, J., Locher, K. P., & Tajkhorshid, E. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2213437120 · Cited by 40 · see citing works
Structure and transport mechanism of the human cholesterol transporter ABCG1
Xu, D., Li, Y., Yang, F., Sun, C.-R., Pan, J., Wang, L., Chen, Z., Fang, S., Yao, X., Hou, W., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110298 · Cited by 38 · see citing works
The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis
Tzanakakis, G. N., Giatagana, E.-M., Berdiaki, A., Spyridaki, I., Hida, K., Neagu, M. T., Tsatsakis, A. M., & Nikitovic, D. (2021) · Cancers · doi:10.3390/cancers13102478 · Cited by 37 · see citing works
Mammalian ABCG-transporters, sterols and lipids: To bind perchance to transport?
Kerr, I. D., Hutchison, E., Gerard, L., Aleidi, S. M., & Gelissen, I. C. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2020.158860 · Cited by 35 · see citing works
Mechanistic basis of breast cancer resistance protein inhibition by new indeno[1,2-b]indoles
Kita, D. H., Guragossian, N., Zattoni, I. F., Moure, V. R., Rego, F. G. D. M., Lusvarghi, S., Moulenat, T., Belhani, B., Picheth, G., Bouacida, S., et al. (2021) · Scientific Reports · doi:10.1038/s41598-020-79892-w · Cited by 35 · see citing works
Molecular insights into the human ABCB6 transporter
Song, G., Zhang, S., Tian, M., Zhang, L., Guo, R., Zhuo, W., & Yang, M. (2021) · Cell Discovery · doi:10.1038/s41421-021-00284-z · Cited by 35 · see citing works
Structure of the Human Cholesterol Transporter ABCG1
Skarda, L., Kowal, J., & Locher, K. P. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167218 · Cited by 35 · see citing works
Teng, Q., Lei, Z., Wang, J., Yang, Y., Wu, Z., Acharekar, N., Zhang, W., Yoganathan, S., Pan, Y., Wurpel, J. N. D., et al. (2023) · Drug Resistance Updates · doi:10.1016/j.drup.2023.101028 · Cited by 34 · see citing works
Medically Important Alterations in Transport Function and Trafficking of ABCG2
Homolya, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062786 · Cited by 34 · see citing works
Moinul, M., Amin, S. A., Jha, T., & Gayen, S. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114628 · Cited by 34 · see citing works
Structures and coordination chemistry of transporters involved in manganese and iron homeostasis
Ray, S., & Gaudet, R. (2023) · Biochemical Society Transactions · doi:10.1042/bst20210699 · Cited by 30 · see citing works
Ji, N., Li, H., Zhang, Y., Li, Y., Wang, P., Chen, X., Liu, Y.-N., Wang, J.-Q., Yang, Y., Chen, Z., et al. (2024) · Drug Resistance Updates · doi:10.1016/j.drup.2024.101100 · Cited by 33 · see citing works
Cryo-EM structure and molecular mechanism of abscisic acid transporter ABCG25
Huang, X., Zhang, X., An, N., Zhang, M., Ma, M., Yang, Y., Jing, L., Wang, Y., Chen, Z., & Zhang, P. (2023) · Nature Plants · doi:10.1038/s41477-023-01509-7 · Cited by 32 · see citing works
Cryo‐EM structures of human ABCA7 provide insights into its phospholipid translocation mechanisms
Le, L. T. M., Thompson, J. R., Dehghani‐Ghahnaviyeh, S., Pant, S., Dang, P. X., French, J. B., Kanikeyo, T., Tajkhorshid, E., & Alam, A. (2023) · The EMBO Journal · doi:10.15252/embj.2022111065 · Cited by 31 · see citing works
Guo, C., Tang, Y., Zhao, Y., Li, G., & Zhang, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.958161 · Cited by 30 · see citing works
Banerjee, A., Pata, J., Sharma, S., Monk, B. C., Falson, P., & Prasad, R. (2021) · Journal of Fungi · doi:10.3390/jof7020068 · Cited by 29 · see citing works
Chandratre, S., Olsen, J., Howley, R., & Chen, B. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115851 · Cited by 30 · see citing works
Picky ABCG5/G8 and promiscuous ABCG2 ‐ a tale of fatty diets and drug toxicity
Khunweeraphong, N., Mitchell, J., Szöllősi, D., Hussein, T. O. K., Kuchler, K., Kerr, I. D., Stockner, T., & Lee, J. (2020) · FEBS Letters · doi:10.1002/1873-3468.13938 · Cited by 29 · see citing works
Nagy, T., Tóth, Á., Telbisz, Á., Sarkadi, B., Tordai, H., Tordai, A., & Hegedűs, T. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03651-3 · Cited by 28 · see citing works
Stefan, E., Obexer, R., Hofmann, S., Huu, K. V., Huang, Y., Morgner, N., Suga, H., & Tampé, R. (2021) · eLife · doi:10.7554/elife.67732 · Cited by 28 · see citing works
Wu, C., Hung, C., Lusvarghi, S., Huang, Y.-H., Tseng, P.-J., Hung, T., Yu, J., & Ambudkar, S. V. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114137 · Cited by 27 · see citing works
Tordai, H., Suhajda, E., Sillitoe, I., Nair, S., Varadi, M., & Hegedus, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23168877 · Cited by 22 · see citing works
Cryo-EM structure of ABCG5/G8 in complex with modulating antibodies
Zhang, H., Huang, C.-S., Yu, X., Lee, J., Vaish, A., Chen, Q., Zhou, M., Wang, Z., & Min, X. (2021) · Communications Biology · doi:10.1038/s42003-021-02039-8 · Cited by 26 · see citing works
Ibrahim, M. A. A., Abdelrahman, A. H. M., Badr, E. A. A., Almansour, N. M., Alzahrani, O. R., Ahmed, M. N., Soliman, M. E. S., Naeem, M. A., Shawky, A. M., Sidhom, P. A., et al. (2022) · Molecular Diversity · doi:10.1007/s11030-022-10389-6 · Cited by 26 · see citing works
Cryo‐EM of ABC transporters: an ice‐cold solution to everything?
Januliene, D., & Moeller, A. (2020) · FEBS Letters · doi:10.1002/1873-3468.13989 · Cited by 26 · see citing works
Wu, Z., Teng, Q., Yang, Y., Acharekar, N., Wang, J., He, M. Y., Yoganathan, S., Lin, J., Wang, J., & Chen, Z. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.12.018 · Cited by 25 · see citing works
Mohammed, H. A., Almahmoud, S. A., Arfeen, M., Srivastava, A., El-Readi, M. Z., Ragab, E. A., Shehata, S. M., Mohammed, S. A. A., Mostafa, E. M., El-Khawaga, H. A. Y., et al. (2022) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2022.103950 · Cited by 25 · see citing works
Ameliorative effect of Lacticaseibacillus rhamnosus Fmb14 from Chinese yogurt on hyperuricemia
Zhao, H., Chen, X., Meng, F., Zhou, L., Pang, X., Lu, Z., & Lu, Y. (2022) · Food Science and Human Wellness · doi:10.1016/j.fshw.2022.10.031 · Cited by 25 · see citing works
Activity and Structural Dynamics of Human ABCA1 in a Lipid Membrane
Plummer, A. M., Culbertson, A., Morales-Pérez, C. L., & Liao, M. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168038 · Cited by 24 · see citing works
Self-citationCao, L., Weng, K., Li, L., Lin, G., Zhao, Y., Gao, Y., Huang, X., Chen, Q., Wang, J., Zheng, C., et al. (2024) · Theranostics · doi:10.7150/thno.98389 · Cited by 23 · see citing works
Dong, X., Zhang, M., Teng, Q., Lei, Z., Cai, C., Wang, J., Wu, Z., Yang, Y., Chen, X., Guo, H., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217309 · Cited by 22 · see citing works
Ibrahim, M. A. A., Badr, E. A. A., Abdelrahman, A. H. M., Almansour, N. M., Shawky, A. M., Mekhemer, G. A. H., Alrumaihi, F., Moustafa, M., & Atia, M. A. M. (2021) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-021-00985-y · Cited by 22 · see citing works
Frozen motion: how cryo-EM changes the way we look at ABC transporters
Shvarev, D., Januliene, D., & Moeller, A. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2021.11.008 · Cited by 22 · see citing works
Banerjee, A., Pata, J., Chaptal, V., Boumendjel, A., Falson, P., & Prasad, R. (2023) · Drug Resistance Updates · doi:10.1016/j.drup.2023.100992 · Cited by 20 · see citing works
Structural and mechanistic basis of substrate transport by the multidrug transporter MRP4
Bloch, M., Raj, I., Pape, T., & Taylor, N. M. I. (2023) · Structure · doi:10.1016/j.str.2023.08.014 · Cited by 21 · see citing works
Vesga, L. C., Kronenberger, T., Tonduru, A. K., Kita, D. H., Zattoni, I. F., Bernal, C. C., Bohórquez, A. R. R., Méndez‐Sánchez, S. C., Ambudkar, S. V., Valdameri, G., et al. (2021) · ChemMedChem · doi:10.1002/cmdc.202100188 · Cited by 20 · see citing works
Overexpression of ABCG2 Confers Resistance to MLN7243, a Ubiquitin-Activating Enzyme (UAE) Inhibitor
Wu, Z., Yang, Y., Wang, J., Narayanan, S., Lei, Z., Teng, Q., Zeng, L., & Chen, Z. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.697927 · Cited by 19 · see citing works
Implication of ABC transporters in non-proliferative diseases
Grigoreva, T. A., Sagaidak, A. V., Novikova, D., & Tribulovich, V. G. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175327 · Cited by 19 · see citing works
Wong, I. L. K., Zhu, X., Chan, K., Liu, Z., Chan, C.-F., Chow, T. S., Chong, T. C., Law, M. C., Cui, J., Chow, L. M. C., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00779 · Cited by 18 · see citing works
The net electrostatic potential and hydration of ABCG2 affect substrate transport
Gose, T., Aitken, H. M., Wang, Y., Lynch, J., Rampersaud, E., Fukuda, Y., Wills, M., Baril, S. A., Ford, R. C., Shelat, A. A., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40610-5 · Cited by 18 · see citing works
Yu, Z.-Z., Xu, B.-Q., Wang, Y.-Y., Zhang, P.-W., Shu, Y.-B., & Shi, Z. (2023) · Biomedicines · doi:10.3390/biomedicines11113103 · Cited by 18 · see citing works
Fan, W., Shao, K., & Luo, M. (2024) · Biomolecules · doi:10.3390/biom14020231 · Cited by 18 · see citing works
Wu, Z., Mai, Q., Yang, Y., Wang, J., Ma, H., Zeng, L., Chen, Z., & Pan, Y. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111223 · Cited by 18 · see citing works
Dakhlaoui, I., Vahdati, S., Maalej, E., Chabchoub, F., Wiese, M., Marco, J. L., & Ismaïli, L. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105326 · Cited by 18 · see citing works
Koide, E., Pietz, H. L., Beltran, J., & Chen, J. (2025) · Nature Communications · doi:10.1038/s41467-024-55810-w · Cited by 17 · see citing works
Culbertson, A., & Liao, M. (2025) · Nature Communications · doi:10.1038/s41467-025-58561-4 · Cited by 17 · see citing works
Self-citationABCG: a new fold of ABC exporters and a whole new bag of riddles!
Banerjee, A., Moréno, A., Pata, J., Falson, P., & Prasad, R. (2020) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2020.09.006 · Cited by 17 · see citing works
Elbahnsi, A., Dudás, B., Callebaut, I., Hinzpeter, A., & Miteva, M. A. (2024) · Pharmaceuticals · doi:10.3390/ph17121602 · Cited by 17 · see citing works
Webb, B. M., Bryson, B. L., Williams-Medina, E., Bobbitt, J. R., Seachrist, D. D., Anstine, L. J., & Keri, R. A. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101162 · Cited by 16 · see citing works
Budagaga, Y., Sabet, Z., Zhang, Y. L., Novotná, E., Hanke, I., Rozkoš, T., & Hofman, J. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115769 · Cited by 15 · see citing works
Narayanan, S., Gujarati, N. A., Wang, J., Wu, Z., Koya, J., Cui, Q., Korlipara, V. L., Ashby, C. R., & Chen, Z. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052463 · Cited by 15 · see citing works
Petersen, M. J., Lund, X. L., Semple, S. J., Buirchell, B. J., Franzyk, H., Gajhede, M., Kongstad, K. T., Stenvang, J., & Stærk, D. (2021) · Biomolecules · doi:10.3390/biom11101534 · Cited by 15 · see citing works
How Cryo-EM Has Expanded Our Understanding of Membrane Transporters
Baril, S. A., Gose, T., & Schuetz, J. D. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.122.001004 · Cited by 14 · see citing works
Ma, H., Xing, F., Zhou, Y., Yu, P., Luo, R., Xu, J., Xiang, Z., Rommens, P. M., Duan, X., & Ritz, U. (2023) · Journal of Materials Chemistry B · doi:10.1039/d3tb01008b · Cited by 14 · see citing works
A Pan-Cancer Landscape of ABCG2 across Human Cancers: Friend or Foe?
Lyu, C., Wang, L., Stadlbauer, B., Büchner, A., & Pohla, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415955 · Cited by 14 · see citing works
Non-coding RNAs in renal cell carcinoma: Implications for drug resistance
Liu, Y., Zhang, H., Fang, Y., Tang, D., & Luo, Z. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115001 · Cited by 14 · see citing works
The Important Role of Transporter Structures in Drug Disposition, Efficacy, and Toxicity
Fu, T., Zeng, S., Zheng, Q., & Zhu, F. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.123.001275 · Cited by 13 · see citing works
Santhanam, M., Pandey, S. K., Shteinfer‐Kuzmine, A., Paul, A., Abusiam, N., Zalk, R., & Shoshan‐Barmatz, V. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.04.007 · Cited by 13 · see citing works
Aptamer-functionalized nanomaterials (AFNs) for therapeutic management of hepatocellular carcinoma
Yin, X., Rong, J., Shao, M., Zhang, S., Yin, L., He, Z., & Wang, X. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02486-5 · Cited by 13 · see citing works
OTS964, a TOPK Inhibitor, Is Susceptible to ABCG2-Mediated Drug Resistance
Yang, Y., Wu, Z., Wang, J., Teng, Q., Lei, Z., Lusvarghi, S., Ambudkar, S. V., Chen, Z., & Yang, D. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.620874 · Cited by 13 · see citing works
AZ32 Reverses ABCG2-Mediated Multidrug Resistance in Colorectal Cancer
Liu, K., Li, Y.-C., Chen, Y., Shi, X., Xing, Z.-H., He, Z.-J., Wang, S.-T., Liu, W., Zhang, P.-W., Yu, Z.-Z., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.680663 · Cited by 13 · see citing works
Wu, C., Hung, C., Hsieh, Y., Murakami, M., Huang, Y.-H., Su, T.-Y., Hung, T., Yu, J., Wu, Y., & Ambudkar, S. V. (2023) · Cells · doi:10.3390/cells12071056 · Cited by 13 · see citing works
Kiełbowski, K., Król, M., Bakinowska, E., & Pawlik, A. (2024) · Membranes · doi:10.3390/membranes14110223 · Cited by 12 · see citing works
ABCG2 Transporter: From Structure to Function—Current Insights and Open Questions
Álvarez–Fernández, L., Millán–García, A., Merino, G., & Blanco–Paniagua, E. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136119 · Cited by 12 · see citing works
Dudás, B., Declèves, X., Cisternino, S., Pérahia, D., & Miteva, M. A. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.07.035 · Cited by 12 · see citing works
Combinatorial Anticancer Drug Screen Identifies Off-Target Effects of Epigenetic Chemical Probes
Barghout, S. H., Mann, M. K., Aman, A. M., Yu, Y., Alteen, M. G., Schimmer, A. D., Schapira, M., Arrowsmith, C. H., & Baršytė-Lovejoy, D. (2022) · ACS Chemical Biology · doi:10.1021/acschembio.2c00451 · Cited by 12 · see citing works
Nucleotide binding is the critical regulator of ABCG2 conformational transitions
Gyöngy, Z., Mocsár, G., Hegedüs, É., Stockner, T., Ritter, Z., Homolya, L., Schamberger, A., Orbán, T. I., Remenyik, J., Szakács, G., et al. (2023) · eLife · doi:10.7554/elife.83976 · Cited by 12 · see citing works
Plastic structures for diverse substrates: A revisit of human ABC transporters
Hou, W., Xu, D., Wang, L., Chen, Y., Chen, Z., Zhou, C., & Chen, Y. (2022) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26406 · Cited by 12 · see citing works
- Authors
- Orlando, B. J., & Liao, M.
- Affiliations
- Harvard University (US)
- Corresponding author
- Liao, Maofu
- Venue
- Nature Communications
- Published
- 2020-05-08
- Volume
- 11
- Issue
- 1
- Pages
- 2264-2264
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7210939
- OpenAlex
- W3021390585
- Cited by
- 198
- References
- 57
- Citations by year
- 2026: 20 · 2025: 18 · 2024: 31 · 2023: 39 · 2022: 31 · 2021: 46 · 2020: 12 · 2019: 1
- FWCI
- 11.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Cancer Society (PF-17-212-01–DMC)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- ABCG2, ABC transporters, multidrug resistance, anticancer drug transport, conformational cycle, imatinib, inward-facing conformation, drug efflux
- MeSH terms
- Imatinib Mesylate, ATP Binding Cassette Transporter, Subfamily G, Member 2, Antineoplastic Agents, Biological Transport, Disulfides, Humans, Ligands, Mitoxantrone, Models, Biological, Protein Structure, Secondary, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
