Adaptive Chromatin Remodeling Drives Glioblastoma Stem Cell Plasticity and Drug Tolerance
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Glioblastoma, the most common and aggressive malignant brain tumor, is propagated by stem-like cancer cells refractory to existing therapies. Understanding the molecular mechanisms that control glioblastoma stem cell (GSC) proliferation and drug resistance may reveal opportunities for therapeutic interventions. Here we show that GSCs can reversibly transition to a slow-cycling, persistent state in response to targeted kinase inhibitors. In this state, GSCs upregulate primitive developmental programs and are dependent upon Notch signaling. This transition is accompanied by widespread redistribution of repressive histone methylation. Accordingly, persister GSCs upregulate, and are dependent on, the histone demethylases KDM6A/B. Slow-cycling cells with high Notch activity and histone demethylase expression are present in primary glioblastomas before treatment, potentially contributing to relapse. Our findings illustrate how cancer cells may hijack aspects of native developmental programs for deranged proliferation, adaptation, and tolerance. They also suggest strategies for eliminating refractory tumor cells by targeting epigenetic and developmental pathways.
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Glioblastoma persister cells depend on Notch signaling upon treatment with the multi-kinase inhibitor dasatinib.
“Liau et al. reported that glioblastoma persister cells depend on Notch signaling upon treatment with the multi-kinase inhibitor dasatinib [45].”
From Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer (2021) · cites this paper as [45]
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Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179 · see citing works
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581 · see citing works
The 2007 WHO Classification of Tumours of the Central Nervous System
Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., Scheithauer, B. W., & Kleihues, P. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0243-4 · Cited by 15,422 · see citing works
ggplot2: Elegant Graphics for Data Analysis
Wickham, H. (2009) · doi:10.1007/978-0-387-98141-3 · Cited by 14,447 · see citing works
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · see citing works
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735 · see citing works
Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.020 · Cited by 7,575 · see citing works
Identification of human brain tumour initiating cells
Singh, S. K., Hawkins, C. E., Clarke, I. D., Squire, J. A., Bayani, J., Hide, T., Henkelman, R. M., Cusimano, M. D., & Dirks, P. B. (2004) · Nature · doi:10.1038/nature03128 · Cited by 7,388 · see citing works
Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
Bao, S., Wu, Q., McLendon, R. E., Hao, Y., Shi, Q., Hjelmeland, A. B., Dewhirst, M. W., Bigner, D. D., & Rich, J. N. (2006) · Nature · doi:10.1038/nature05236 · Cited by 6,363 · see citing works
Self-citationSingle-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
Patel, A. P., Tirosh, I., Trombetta, J. J., Shalek, A. K., Gillespie, S. M., Wakimoto, H., Cahill, D. P., Nahed, B. V., Curry, W. T., Martuza, R. L., et al. (2014) · Science · doi:10.1126/science.1254257 · Cited by 5,063 · see citing works
Self-citationThe Somatic Genomic Landscape of Glioblastoma
Brennan, C. W., Verhaak, R. G. W., McKenna, A., Campos, B., Noushmehr, H., Salama, S. R., Zheng, S., Chakravarty, D., Sanborn, J. Z., Berman, S. H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.034 · Cited by 5,016 · see citing works
Software for Computing and Annotating Genomic Ranges
Lawrence, M. F., Huber, W. K., Pagès, H., Aboyoun, P., Carlson, M. R. J., Gentleman, R. C., Morgan, M. T., & Carey, V. J. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003118 · Cited by 4,438 · see citing works
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137 · see citing works
The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism
Kopan, R., & Ilagan, M. X. G. (2009) · Cell · doi:10.1016/j.cell.2009.03.045 · Cited by 3,631 · see citing works
A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaran, S., McDermott, U., Azizian, N., Zou, L., Fischbach, M. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.02.027 · Cited by 2,770 · see citing works
Lee, J., Kotliarova, S. E., Kotliarov, Y., Li, A., Su, Q., Donin, N. M., Pastorino, S., Purow, B. W., Christopher, N., Zhang, W., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.030 · Cited by 2,289 · see citing works
A restricted cell population propagates glioblastoma growth after chemotherapy
Chen, J., Li, Y., Yu, T.-S., McKay, R. M., Burns, D. K., Kernie, S. G., & Parada, L. F. (2012) · Nature · doi:10.1038/nature11287 · Cited by 2,096 · see citing works
Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation
Doench, J. G., Hartenian, E., Graham, D. B., Tothova, Z., Hegde, M., Smith, I., Sullender, M., Ebert, B. L., Xavier, R. J., & Root, D. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.3026 · Cited by 1,617 · see citing works
Cancer stem cells in glioblastomaPreprint
Lathia, J. D., Mack, S. C., Mulkearns-Hubert, E. E., Valentim, C. L. L., & Rich, J. N. (2015) · Genes & Development · doi:10.1101/gad.261982.115 · Cited by 1,600 · see citing works
Self-citationRoesch, A., Fukunaga‐Kalabis, M., Schmidt, E. C., Zabierowski, S. E., Brafford, P. A., Vultur, A., Basu, D., Gimotty, P. A., VOGT, T. M., & Herlyn, M. (2010) · Cell · doi:10.1016/j.cell.2010.04.020 · Cited by 1,162 · see citing works
ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data
Zhu, L., Gazin, C., Lawson, N., Pagès, H., Lin, S. M., Lapointe, D. S., & Green, M. R. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-237 · Cited by 1,144 · see citing works
Mechanisms of disseminated cancer cell dormancy: an awakening field
Sosa, M. S., Bragado, P., & Aguirre‐Ghiso, J. A. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3793 · Cited by 1,125 · see citing works
De Santa, F., Totaro, M. G., Prosperini, E., Notarbartolo, S., Testa, G., & Natoli, G. (2007) · Cell · doi:10.1016/j.cell.2007.08.019 · Cited by 965 · see citing works
A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response
Kruidenier, L., Chung, C.-W., Cheng, Z., Liddle, J., Che, K., Joberty, G., Bantscheff, M., Bountra, C., Bridges, A., Diallo, H., et al. (2012) · Nature · doi:10.1038/nature11262 · Cited by 950 · see citing works
Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells
Suvà, M. L., Rheinbay, E., Gillespie, S. M., Patel, A. P., Wakimoto, H., Rabkin, S. D., Riggi, N., Chi, A. S., Cahill, D. P., Nahed, B. V., et al. (2014) · Cell · doi:10.1016/j.cell.2014.02.030 · Cited by 927 · see citing works
Self-citationCancer Epigenetics: Tumor Heterogeneity, Plasticity of Stem-like States, and Drug Resistance
Easwaran, H., Tsai, H.-C., & Baylin, S. B. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.015 · Cited by 915 · see citing works
Shen, L., Shao, N., Liu, X., & Nestler, E. J. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-284 · Cited by 852 · see citing works
Llorens-Bobadilla, E., Zhao, S., Baser, A., Saiz-Castro, G., Zwadlo, K., & Martin-Villalba, A. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.07.002 · Cited by 778 · see citing works
Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains
Shi, J., Wang, E., Milazzo, J. P., Wang, Z., Kinney, J. B., & Vakoc, C. R. (2015) · Nature Biotechnology · doi:10.1038/nbt.3235 · Cited by 739 · see citing works
Simon, J. A., & Kingston, R. E. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.02.013 · Cited by 727 · see citing works
Imayoshi, I., Sakamoto, M., Yamaguchi, M., Mori, K., & Kageyama, R. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4987-09.2010 · Cited by 716 · see citing works
Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA
Nathanson, D. A., Gini, B., Mottahedeh, J., Visnyei, K., Koga, T., Gomez, G. G., Eskin, A., Hwang, K., Wang, J., Masui, K., et al. (2013) · Science · doi:10.1126/science.1241328 · Cited by 699 · see citing works
SSEA-1 Is an Enrichment Marker for Tumor-Initiating Cells in Human Glioblastoma
Son, M. J., Woolard, K., Nam, D., Lee, J., & Fine, H. A. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.03.003 · Cited by 672 · see citing works
Roesch, A., Vultur, A., Bogeski, I., Wang, H., Zimmermann, K. M., Speicher, D., Körbel, C., Laschke, M. W., Gimotty, P. A., Philipp, S. E., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.05.003 · Cited by 670 · see citing works
Codega, P., Silva-Vargas, V., Paul, A., Maldonado-Soto, A. R., DeLeo, A. M., Pastrana, E., & Doetsch, F. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.039 · Cited by 634 · see citing works
FoxO3 Regulates Neural Stem Cell Homeostasis
Renault, V. M., Rafalski, V. A., Morgan, A. A., Salih, D. A. M., Brett, J. O., Webb, A. E., Villeda, S. A., Thekkat, P. U., Guillerey, C., Denko, N. C., et al. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.09.014 · Cited by 586 · see citing works
Gangemi, R. M. R., Griffero, F., Marubbi, D., Perera, M., Capra, M. C., Malatesta, P., Ravetti, G. L., Zona, G., Daga, A., & Corte, G. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0493 · Cited by 578 · see citing works
Genome-wide chromatin state transitions associated with developmental and environmental cues
Zhu, J., Adli, M., Zou, J., Verstappen, G., Coyne, M. J., Zhang, X.-L., Durham, T. J., Miri, M., Deshpande, V., Jager, P. D., et al. (2013) · Cell · doi:10.1016/j.cell.2012.12.033 · Cited by 553 · see citing works
Self-citationIkushima, H., Todo, T., Ino, Y., Takahashi, M., Miyazawa, K., & Miyazono, K. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.08.018 · Cited by 540 · see citing works
Differential Notch signalling distinguishes neural stem cells from intermediate progenitors
Mizutani, K., Yoon, K., Dang, L. T., Tokunaga, A., & Gaiano, N. (2007) · Nature · doi:10.1038/nature06090 · Cited by 521 · see citing works
Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal
Aguirre, A. A., Rubio, M. E., & Gallo, V. (2010) · Nature · doi:10.1038/nature09347 · Cited by 482 · see citing works
Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma
Hashizume, R., Andor, N., Ihara, Y., Lerner, R., Gan, H., Chen, X., Fang, D., Huang, X., Tom, M. W., Ngo, V., et al. (2014) · Nature Medicine · doi:10.1038/nm.3716 · Cited by 476 · see citing works
FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis
Paik, J.-H., Ding, Z., Narurkar, R., Ramkissoon, S., Muller, F., Kamoun, W. S., Chae, S.-S., Zheng, H., Ying, H., Mahoney, J., et al. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.09.013 · Cited by 459 · see citing works
Agger, K., Cloos, P. A. C., Rudkjær, L., Williams, K., Andersen, G., Christensen, J., & Helin, K. (2009) · Genes & Development · doi:10.1101/gad.510809 · Cited by 427 · see citing works
Xia, X., Lemieux, M. E., Li, W., Carroll, J. S., Brown, M., Liu, X. S., & Kung, A. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810067106 · Cited by 410 · see citing works
Heterodimeric JAK–STAT activation as a mechanism of persistence to JAK2 inhibitor therapy
Koppikar, P., Bhagwat, N., Kilpivaara, O., Manshouri, T., Adli, M., Hricik, T., Liu, F., Saunders, L. M., Mullally, A., Abdel-Wahab, O. I., et al. (2012) · Nature · doi:10.1038/nature11303 · Cited by 370 · see citing works
Self-citationAn epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia
Knoechel, B., Roderick, J. E., Williamson, K. E., Zhu, J., Lohr, J. G., Cotton, M. J., Gillespie, S. M., Fernandez, D. E., Ku, M., Wang, H., et al. (2014) · Nature Genetics · doi:10.1038/ng.2913 · Cited by 369 · see citing works
Self-citationContrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia
Ntziachristos, P., Tsirigos, A., Welstead, G. G., Trimarchi, T., Bakogianni, S., Xu, L., Loizou, E., Holmfeldt, L., Strikoudis, A., King, B., et al. (2014) · Nature · doi:10.1038/nature13605 · Cited by 366 · see citing works
Wakimoto, H., Kesari, S., Farrell, C. J., Curry, W. T., Zaupa, C., Aghi, M. K., Kuroda, T., Stemmer-Rachamimov, A. O., Shah, K., Liu, T., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3886 · Cited by 361 · see citing works
Self-citationDiagnostic and therapeutic avenues for glioblastoma: no longer a dead end?
Tanaka, S., Louis, D. N., Curry, W. T., Batchelor, T. T., & Dietrich, J. (2012) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2012.204 · Cited by 308 · see citing works
Vanner, R. J., Remke, M., Gallo, M., Selvadurai, H. J., Coutinho, F. J., Lee, L., Kushida, M. M., Head, R., Morrissy, A. S., Zhu, X., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.05.005 · Cited by 306 · see citing works
Mastermind critically regulates Notch-mediated lymphoid cell fate decisions
Maillard, I. P., Weng, A. P., Carpenter, A. C., Rodríguez, C. G., Sai, H., Xu, L., Allman, D., Aster, J. C., & Pear, W. S. (2004) · Blood · doi:10.1182/blood-2004-02-0514 · Cited by 284 · see citing works
Self-citationRheinbay, E., Suvà, M. L., Gillespie, S. M., Wakimoto, H., Patel, A. P., Shahid, M., Oksuz, O., Rabkin, S. D., Martuza, R. L., Rivera, M. N., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.04.021 · Cited by 268 · see citing works
Self-citationThe Genotype-Tissue Expression (GTEx) project
Lonsdale, J., Thomas, J., Salvatore, M., Phillips, R., Lo, E., Shad, S., Hasz, R., Walters, G., Garcia, F., Young, N., et al. (2013) · Nature Genetics · doi:10.1038/ng.2653 · Cited by 263 · see citing works
Wang, H., Zou, J., Zhao, B., Johannsen, E., Ashworth, T. D., Wong, H., Pear, W. S., Schug, J., Blacklow, S. C., Arnett, K. L., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109023108 · Cited by 233 · see citing works
Self-citationInhibition of demethylases by GSK-J1/J4
Heinemann, B., Nielsen, J. M., Hudlebusch, H. R., Lees, M. J., Larsen, D. V., Boesen, T. P., Labelle, M., Gerlach, L., Birk, P., & Helin, K. (2014) · Nature · doi:10.1038/nature13688 · Cited by 230 · see citing works
Mechanistic Insights into Notch Receptor Signaling from Structural and Biochemical Studies
Kovall, R. A., & Blacklow, S. C. (2010) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(10)92002-4 · Cited by 213 · see citing works
Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescencePreprint
Martynoga, B., Mateo, J. L., Zhou, B., Andersen, J., Achimastou, A., Urbán, N., van den Berg, D. L. C., Georgopoulou, D., Hadjur, S., Wittbrodt, J., et al. (2013) · Genes & Development · doi:10.1101/gad.216804.113 · Cited by 204 · see citing works
Structural analysis of human KDM5B guides histone demethylase inhibitor development
Johansson, C., Velupillai, S., Tumber, A., Szykowska, A., Hookway, E. S., Nowak, R. P., Strain-Damerell, C. M., Gileadi, C., Philpott, M., Burgess-Brown, N., et al. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2087 · Cited by 200 · see citing works
Mehta, S. V., Huillard, E., Kesari, S., Maire, C. L., Golebiowski, D., Harrington, E. P., Alberta, J. A., Kane, M., Theisen, M., Ligon, K. L., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.01.035 · Cited by 158 · see citing works
Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
Xu, R., Shimizu, F., Hovinga, K. E., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0048 · Cited by 129 · see citing works
Dewaele, B., Wasąg, B., Cools, J., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0533 · Cited by 121 · see citing works
Ene, C., Edwards, L., Riddick, G., Baysan, M. S., Woolard, K., Kotliarova, S. E., Lai, C., Belova, G. I., Cam, M. C., Walling, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051407 · Cited by 110 · see citing works
The role of Notch signaling in adult neurogenesis
Imayoshi, I., & Kageyama, R. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8186-0 · Cited by 102 · see citing works
A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes
Giachino, C., Boulay, J., Ivánek, R., Alvarado, A. G., Tostado, C., Lugert, S., Tchorz, J. S., Coban, M., Mariani, L., Bettler, B., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.10.008 · Cited by 102 · see citing works
Molecular Heterogeneity of Glioblastoma and its Clinical Relevance
Éder, K., & Kálmán, B. (2014) · Pathology & Oncology Research · doi:10.1007/s12253-014-9833-3 · Cited by 100 · see citing works
Tamura, K., Aoyagi, M., Ando, N., Ogishima, T., Wakimoto, H., Yamamoto, M., & Ohno, K. (2013) · Journal of neurosurgery · doi:10.3171/2013.7.jns122417 · Cited by 96 · see citing works
Self-citationWilliams, K., Christensen, J. F., Rappsilber, J., Nielsen, A. L., Johansen, J. V., & Helin, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096545 · Cited by 88 · see citing works
Leng, N., Li, Y., McIntosh, B. E., Nguyen, B. K., Duffin, B. M., Tian, S., Thomson, J. A., Dewey, C. N., Stewart, R. M., & Kendziorski, C. M. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv193 · Cited by 85 · see citing works
Hypoxia drives transient site-specific copy gain and drug-resistant gene expressionPreprint
Black, J. C., Atabakhsh, E., Kim, J., Biette, K. M., Rechem, C. V., Ladd, B., Burrowes, P. D., Donado, C. A., Mattoo, H., Kleinstiver, B. P., et al. (2015) · Genes & Development · doi:10.1101/gad.259796.115 · Cited by 83 · see citing works
A role for the transcription factor HEY1 in glioblastoma
Hulleman, E., Quarto, M., Vernell, R., Masserdotti, G., Colli, E., Kros, J. M., Levi, D., Gaetani, P., Tunici, P., Finocchiaro, G., et al. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00307.x · Cited by 83 · see citing works
Yahyanejad, S., King, H., Iglesias, V. S., Granton, P. V., Barbeau, L. M. O., van Hoof, S. J., Groot, A. J., Habets, R., Prickaerts, J., Chalmers, A. J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9275 · Cited by 80 · see citing works
Black, B. L., Ligon, K. L., Zhang, Y., & Olson, E. N. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.43.26659 · Cited by 75 · see citing works
Cenciarelli, C., Marei, H. E. S., Zonfrillo, M., Pierimarchi, P., Paldino, E., Casalbore, P., Felsani, A., Vescovi, A. L., Maira, G., & Mangiola, A. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-247 · Cited by 59 · see citing works
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Epigenetic plasticity and the hallmarks of cancer
Flavahan, W. A., Gaskell, E., & Bernstein, B. E. (2017) · Science · doi:10.1126/science.aal2380 · Cited by 1,340 · see citing works
Self-citationWen, P. Y., Weller, M., Lee, E. Q., Alexander, B. M., Barnholtz-Sloan, J. S., Barthel, F. P., Batchelor, T. T., Bindra, R. S., Chang, S. M., Chiocca, E. A., et al. (2020) · Neuro-Oncology · doi:10.1093/neuonc/noaa106 · Cited by 1,168 · see citing works
Stem cell programs in cancer initiation, progression, and therapy resistance
Huang, T., Song, X., Xu, D., Tiek, D., Goenka, A., Wu, B., Sastry, N., Hu, B., & Cheng, S.-Y. (2020) · Theranostics · doi:10.7150/thno.41648 · Cited by 524 · see citing works
Targeting Cancer Stemness in the Clinic: From Hype to Hope
Saygin, C., Matei, D., Majeti, R., Reizes, O., & Lathia, J. D. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2018.11.017 · Cited by 517 · see citing works
Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy
Rehman, S. K., Haynes, J., Collignon, E., Brown, K. R., Wang, Y., Nixon, A. M. L., Bruce, J. P., Wintersinger, J. A., Singh Mer, A., Lo, E. B. L., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.018 · Cited by 495 · see citing works
Tumor cell plasticity in targeted therapy-induced resistance: Mechanisms and new strategies
Shi, Z.-D., Pang, K., Wu, Z.-X., Dong, Y., Hao, L., Qin, J.-X., Wang, W., Chen, Z.-S., & Han, C.-H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01383-x · Cited by 256 · see citing works
Slide-tags enables single-nucleus barcoding for multimodal spatial genomics
Russell, A. J. C., Weir, J. A., Nadaf, N. M., Shabet, M., Kumar, V., Kambhampati, S., Raichur, R., Marrero, G. J., Liu, S., Balderrama, K. S., et al. (2024) · Nature · doi:10.1038/s41586-023-06837-4 · Cited by 225 · see citing works
Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer
Cabanos, H. F., & Hata, A. N. (2021) · Cancers · doi:10.3390/cancers13112666 · Cited by 189 · see citing works
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities
Russo, M., Chen, M., Mariella, E., Peng, H., Rehman, S. K., Sancho, E., Sogari, A., Toh, T. S., Balaban, N. Q., Batlle, E., et al. (2024) · Nature Reviews Cancer · doi:10.1038/s41568-024-00737-z · Cited by 210 · see citing works
Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression
Wu, S. J., Furlan, S. N., Mihalas, A. B., Kaya-Okur, H. S., Feroze, A. H., Emerson, S. N., Zheng, Y., Carson, K., Cimino, P. J., Keene, C. D., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00865-z · Cited by 201 · see citing works
Self-citationDifferentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer
Risom, T., Langer, E. M., Chapman, M. P., Rantala, J., Fields, A. J., Boniface, C., Alvarez, M. J., Kendsersky, N. D., Pelz, C. R., Johnson-Camacho, K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05729-w · Cited by 174 · see citing works
Epigenetic modifications: Key players in cancer heterogeneity and drug resistance
Sadida, H. Q., Abdulla, A., Marzooqi, S. A., Hashem, S., Macha, M. A., Akil, A. S. A.-S., & Bhat, A. A. (2024) · Translational Oncology · doi:10.1016/j.tranon.2023.101821 · Cited by 151 · see citing works
Drug resistance in colorectal cancer: An epigenetic overview
Luo, M., Yang, X., Chen, H.-N., Nice, E. C., & Huang, C. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188623 · Cited by 94 · see citing works
Zhang, X., Ma, Y., Ma, J., Yang, L., Song, Q., Wang, H., & Lv, G. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.913669 · Cited by 57 · see citing works
Nonredundant, isoform-specific roles of HDAC1 in glioma stem cells
Lo Cascio, C., McNamara, J. B., Melendez, E. L., Lewis, E. M., Dufault, M. E., Sanai, N., Plaisier, C. L., & Mehta, S. (2021) · JCI Insight · doi:10.1172/jci.insight.149232 · Cited by 33 · see citing works
Cancer Cells Enter an Adaptive Persistence to Survive Radiotherapy and Repopulate Tumor
Zhao, Y., Lu, T., Song, Y., Wen, Y., Deng, Z., Fan, J., Zhao, M., Zhao, R., Luo, Y., xie, J., et al. (2023) · Advanced Science · doi:10.1002/advs.202204177 · Cited by 29 · see citing works
El Meouche, I., Jain, P., Jolly, M. K., & Capp, J.-P. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.102069 · Cited by 22 · see citing works
Notch receptor/ligand diversity: contribution to colorectal cancer stem cell heterogeneity
Brisset, M., Mehlen, P., Meurette, O., & Hollande, F. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1231416 · Cited by 20 · see citing works
- Authors
- Liau, B. B., Sievers, C., Donohue, L. K., Gillespie, S. M., Flavahan, W. A., Miller, T. E., Venteicher, A. S., Hebert, C. H., Carey, C. D., Rodig, S. J., Shareef, S. J., Najm, F. J., van Galen, P., Wakimoto, H., Cahill, D. P., Rich, J. N., Aster, J. C., Suvà, M. L., Patel, A. P., & Bernstein, B. E.
- Affiliations
- Broad Institute (US)
- Cleveland Clinic (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Patel, Anoop P.
- Bernstein, Bradley E.
- ORCID
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 20
- Issue
- 2
- Pages
- 233-246.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC5291795
- OpenAlex
- W2561012755
- Cited by
- 535
- References
- 78
- Citations by year
- 2026: 42 · 2025: 58 · 2024: 55 · 2023: 68 · 2022: 67 · 2021: 85 · 2020: 58 · 2019: 49 · 2018: 30 · 2017: 22
- FWCI
- 24.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 366 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Howard Hughes Medical Institute
- American Brain Tumor Association
- American Cancer Society
- National Brain Tumor Society
- National Human Genome Research Institute
- European Molecular Biology Organization (ALTF 654-2014)
- National Cancer Institute (P50CA165962)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (ALTF 1207-2014)
- National Institutes of Health
- Jane Coffin Childs Memorial Fund for Medical Research
- National Institute of Neurological Disorders and Stroke (R25NS065743)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- glioblastoma, glioblastoma stem cells, drug resistance, chromatin remodeling, Notch signaling, histone demethylase, KDM6A, KDM6B, histone methylation, slow-cycling cells, cancer stem cell plasticity, kinase inhibitors, tumor recurrence, epigenetic therapy
- MeSH terms
- Acetylation, Base Sequence, Brain, Cell Cycle, Enhancer Elements, Genetic, Glioblastoma, Histones, Humans, Lysine, Methylation, Nuclear Proteins, Protein Binding, Protein Kinases, Transcription, Genetic, Biomarkers, Tumor, Neoplastic Stem Cells, Signal Transduction, Drug Resistance, Neoplasm, Chromatin Assembly and Disassembly, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Receptors, Notch, Histone Demethylases, Jumonji Domain-Containing Histone Demethylases
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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.
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