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Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability
Open accessAbstract
Have cancer stem cells MET their match?: Solid tumors have been hypothesized to contain a subset of highly aggressive cells that fuel tumor growth and metastasis. The search is on for drugs that selectively kill or diminish the malignant properties of these tumor-initiating cells (TICs; previously called “cancer stem cells”). Pattabiraman et al. hypothesized that compounds that induce TICs to undergo a phenotypic change called the mesenchymal-to-epithelial transition (MET) would therefore cause TICs to lose their tumor-initiating ability. Indeed, drugs activating the protein kinase A signaling pathway triggered an epigenetic reprogramming of TICs that resulted in the cells acquiring a more benign epithelial-like phenotype. Science , this issue p. 10.1126/science.aad3680
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Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
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
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
Prospective identification of tumorigenic breast cancer cells
Al‐Hajj, M., Wicha, M. S., Benito‐Hernández, A., Morrison, S. J., & Clarke, M. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0530291100 · Cited by 10,579
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Mani, S. A., Guo, W., Liao, M.-J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., Brooks, M. W., Reinhard, F., Zhang, C. C., Shipitsin, M. V., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.027 · Cited by 8,839
Self-citationRegulatory networks defining EMT during cancer initiation and progression
Craene, B. D., & Berx, G. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3447 · Cited by 2,487
Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133
Gonzalez, G. A., & Montminy, M. (1989) · Cell · doi:10.1016/0092-8674(89)90013-5 · Cited by 2,464
Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
Gupta, P. B., Önder, T. T., Jiang, G., Tao, K. X., Kuperwasser, C., Weinberg, R. A., & Lander, E. S. (2009) · Cell · doi:10.1016/j.cell.2009.06.034 · Cited by 2,429
Self-citationIn vitro propagation and transcriptional profiling of human mammary stem/progenitor cellsPreprint
Dontu, G., Abdallah, W. M., Foley, J. M., Jackson, K. W., Clarke, M. F., Kawamura, M., & Wicha, M. S. (2003) · Genes & Development · doi:10.1101/gad.1061803 · Cited by 2,413
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 2,354
Evolution of the Cancer Stem Cell Model
Kreso, A., & Dick, J. E. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.006 · Cited by 2,304
Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
de Rooij, J., Zwartkruis, F. J. T., Verheijen, M. H. G., Cool, R. H., Nijman, S. M. B., Wittinghofer, A., & Bos, J. L. (1998) · Nature · doi:10.1038/24884 · Cited by 1,970
Intrinsic Resistance of Tumorigenic Breast Cancer Cells to Chemotherapy
Li, X., Lewis, M. T., Huang, J., Gutiérrez, C., Osborne, C. K., Wu, M.-F., Hilsenbeck, S. G., Pavlick, A. C., Zhang, X., Chamness, G. C., et al. (2008) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn123 · Cited by 1,789
Generation of Breast Cancer Stem Cells through Epithelial-Mesenchymal Transition
Morel, A., Lièvre, M., Thomas, C., Hinkal, G. W., Ansieau, S., & Puisieux, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002888 · Cited by 1,725
Guy, C. T., Cardiff, R., & Muller, W. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.954-961.1992 · Cited by 1,710
Loss of E-Cadherin Promotes Metastasis via Multiple Downstream Transcriptional Pathways
Önder, T. T., Gupta, P. B., Mani, S. A., Yang, J., Lander, E. S., & Weinberg, R. A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2938 · Cited by 1,557
Self-citationSoule, H. D., Maloney, T., Wolman, S. R., Peterson, W., Brenz, R., McGrath, C. M., Russo, J., Pauley, R. J., Jones, R. F., & Brooks, S. C. (1990) · PubMed · Cited by 1,527
Guy, C. T., Cardiff, R. D., & Muller, W. J. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.954 · Cited by 1,523
Tackling the cancer stem cells — what challenges do they pose?
Pattabiraman, D. R., & Weinberg, R. A. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4253 · Cited by 1,013
Self-citationSlug and Sox9 Cooperatively Determine the Mammary Stem Cell State
Guo, W., Keckesova, Z., Donaher, J. L., Shibue, T., Tischler, V., Reinhardt, F., Itzkovitz, S., Noske, A., Zürrer‐Härdi, U., Bell, G. W., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.008 · Cited by 1,005
Self-citationSelective Killing of Mixed Lineage Leukemia Cells by a Potent Small-Molecule DOT1L Inhibitor
Daigle, S. R., Olhava, E. J., Therkelsen, C. A., Majer, C. R., Sneeringer, C. J., Song, J. J., Johnston, L. D., Scott, M. P., Smith, J. J., Xiao, Y., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.009 · Cited by 926
Cyclic nucleotide research — still expanding after half a century
Beavo, J. A., & Brunton, L. L. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm911 · Cited by 906
Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
Elenbaas, B., Spirio, L., Koerner, F., Fleming, M. D., Zimonjic, D. B., Donaher, J. L., Popescu, N. C., Hahn, W. C., & Weinberg, R. A. (2001) · Genes & Development · doi:10.1101/gad.828901 · Cited by 878
Self-citationShen, L., Shao, N., Liu, X., & Nestler, E. J. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-284 · Cited by 866
Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A
Taskén, K., & Aandahl, E. M. (2004) · Physiological Reviews · doi:10.1152/physrev.00021.2003 · Cited by 807
A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
Enserink, J. M., Christensen, A. E., de Rooij, J., van Triest, M., Schwede, F., Genieser, H. G., Døskeland, S. O., Blank, J. L., & Bos, J. L. (2002) · Nature Cell Biology · doi:10.1038/ncb874 · Cited by 625
Johannessen, M., Delghandi, M. P., & Moens, U. L. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.05.001 · Cited by 586
Gene expression profiling of breast cell lines identifies potential new basal markers
Charafe‐Jauffret, E., Ginestier, C., Monville, F., Finetti, P., Adélaı̈de, J., Cervera, N., Fekairi, S., Xerri, L., Jacquemier, J. D., Birnbaum, D., et al. (2005) · Oncogene · doi:10.1038/sj.onc.1209254 · Cited by 571
Assembly of allosteric macromolecular switches: lessons from PKA
Taylor, S. S., Ilouz, R., Zhang, P., & Kornev, A. P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3432 · Cited by 487
Cyclic AMP in relation to proliferation of the Epidermal cell: a new view
Green, H. (1978) · Cell · doi:10.1016/0092-8674(78)90265-9 · Cited by 481
Dong, C., Wu, Y., Yao, J., Wang, Y., Yu, Y., Rychahou, P. G., Evers, B. M., & Zhou, B. P. (2012) · Journal of Clinical Investigation · doi:10.1172/jci57349 · Cited by 479
CEAS: cis-regulatory element annotation system
Shin, H., Liu, T., Manrai, A. K., & Liu, X. S. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp479 · Cited by 461
Physiological Substrates of cAMP-Dependent Protein Kinase
Shabb, J. B. (2001) · Chemical Reviews · doi:10.1021/cr000236l · Cited by 378
Ellenrieder, V., Hendler, S. F., Boeck, W., Seufferlein, T., Menke, A., Ruhland, C., Adler, G., & Gress, T. M. (2001) · PubMed · Cited by 361
Protein Kinase C α Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells
Tam, W. L., Lu, H., Buikhuisen, J. Y., Soh, B.-S., Lim, E., Reinhardt, F., Wu, Z. J., Krall, J. A., Bierie, B., Guo, W., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.08.005 · Cited by 322
Self-citationDistinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines
Hollestelle, A., Nagel, J. H. A., Smid, M., Lam, S., Elstrodt, F., Wasielewski, M., Ng, S. S., French, P. J., Peeters, J. K., Rozendaal, M. J., et al. (2009) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0460-8 · Cited by 308
Ahmed, N., Abubaker, K., Findlay, J., & Quinn, M. A. (2010) · Current Cancer Drug Targets · doi:10.2174/156800910791190175 · Cited by 237
Chen, C., Yan, W., Hummel, M., Hoffmann, T. K., Gross, M., Kaufmann, A. M., & Albers, A. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016466 · Cited by 235
Mechanisms of transcriptional repression by histone lysine methylation
Hublitz, P., Albert, M., Hfmpeters, A., Hublitz, P., Albert, M., & Peters, A. H. F. M. (2009) · The International Journal of Developmental Biology · doi:10.1387/ijdb.082717ph · Cited by 215
PKA-dependent regulation of the histone lysine demethylase complex PHF2–ARID5B
Baba, A., Ohtake, F., Okuno, Y., Yokota, K., Okada, M., Imai, Y., Ni, M., Meyer, C. A., Igarashi, K., Kanno, J., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2228 · Cited by 200
MEYER, R. B. J., & Miller, J. P. (1974) · Life Sciences · doi:10.1016/0024-3205(74)90228-8 · Cited by 153
Iglesias‐Bartolomé, R., Torres, D., Marone, R., Feng, X., Martı́n, D., Simaan, M., Chen, M., Weinstein, L. S., Taylor, S. S., Molinolo, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3164 · Cited by 147
Quantification of regenerative potential in primary human mammary epithelial cells
Linnemann, J. R., Miura, H., Meixner, L. K., Irmler, M., Kloos, U. J., Hirschi, B., Bartsch, H. S., Sass, S., Beckers, J., Theis, F. J., et al. (2015) · Development · doi:10.1242/dev.123554 · Cited by 146
Orellana, S. A., & McKnight, G. S. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.10.4726 · Cited by 134
Wu, D., Zhau, H. E., Huang, W.-C., Iqbal, S. A., Habib, F. K., Sartor, O. A., Cvitanovic, L., Marshall, F. F., Xu, Z., & Chung, L. W. K. (2007) · Oncogene · doi:10.1038/sj.onc.1210316 · Cited by 134
Anastassiou, D., Rumjantseva, V., Cheng, W., Huang, J., Canoll, P., Yamashiro, D. J., & Kandel, J. J. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-529 · Cited by 133
Sheng, T., Chi, S., Zhang, X., & Xie, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500300200 · Cited by 125
Taylor‐Papadimitriou, J., Purkis, P. E., & Fentiman, I. S. (1980) · Journal of Cellular Physiology · doi:10.1002/jcp.1041020306 · Cited by 125
Amieux, P. S., Howe, D. G., Knickerbocker, H., Lee, D. C., Su, T. T., Laszlo, G. S., Idzerda, R. L., & McKnight, G. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200302200 · Cited by 111
Shaikh, D., Zhou, Q., Chen, T., Ibe, J. C. F., Raj, J. U., & Zhou, G. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.08.007 · Cited by 95
MacPherson, M. R., Molina, P., Souchelnytskyi, S., Wernstedt, C., Martı́n-Pérez, J., Portillo, F., & Cano, A. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-06-0504 · Cited by 74
Singh, R., Shankar, B. S., & Sainis, K. B. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.03.028 · Cited by 65
PROPPER, D. J., Saunders, M. P., Salisbury, A. J., Long, L., O'Byrne, K. J., Braybrooke, J. P., Dowsett, M., Taylor, M., Talbot, D. C., Ganesan, T. S., et al. (1999) · PubMed · Cited by 57
Cyclic Nucleotide‐Gated Channels: Molecular Mechanisms of Activation
Broillet, M.-C., & Firestein, S. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb11352.x · Cited by 55
Growth properties and tumorigenesis of MCF-7 cells transfected with isogenic mutants of rasH.
Sommers, C. L., Papageorge, A. G., Wilding, G., & Gelmann, E. P. (1990) · PubMed · Cited by 50
Nadella, K. S., Jones, G. N., Trimboli, A. J., Stratakis, C. A., Leone, G. W., & Kirschner, L. S. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6002 · Cited by 37
Saunders, M. P., Salisbury, A. J., O'Byrne, K. J., Long, L., Whitehouse, R. M., Talbot, D. C., Mawer, E. B., & Harris, A. L. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4410 · Cited by 26
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Metadata
- Authors
- Pattabiraman, D. R., Bierie, B., Kober, K. I., Thiru, P., Krall, J. A., Zill, C., Reinhardt, F., Tam, W. L., & Weinberg, R. A.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Weinberg, Robert A.
- ORCID
- Venue
- Science
- Published
- 2016-03-04
- Volume
- 351
- Issue
- 6277
- Pages
- aad3680-aad3680
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5131720
- OpenAlex
- W2289283229
- Cited by
- 332
- References
- 60
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 32 · 2023: 26 · 2022: 35 · 2021: 36 · 2020: 47 · 2019: 32 · 2018: 36 · 2017: 41 · 2016: 18
- FWCI
- 22.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- National Health and Medical Research Council of Australia (NHMRC APP1071853)
- National Research Foundation, Singapore (NRF-NRFF2015-04)
- National Medical Research Council, Singapore (NMRC/TCR/007-NCC/2013)
- Ludwig Center for Molecular Oncology at MIT
- Breast Cancer Research Foundation
- Samuel Waxman Cancer Research Foundation
- NIH (R01-CA078461)
- American Cancer Society
- D. K. Ludwig Foundation Cancer Research
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- protein kinase A, mesenchymal-epithelial transition, cancer stem cells, PHF2, histone demethylase, epigenetic reprogramming, cAMP signaling, mammary epithelial cells, differentiation therapy
- MeSH terms
- Adenosine Monophosphate, Animals, Breast Neoplasms, Cell Transformation, Neoplastic, Cholera Toxin, Enzyme Activation, Epithelial Cells, Female, Colforsin, Humans, Mesoderm, Neoplastic Stem Cells, Second Messenger Systems, Cyclic AMP-Dependent Protein Kinases, Homeodomain Proteins, Xenograft Model Antitumor Assays, Mammary Glands, Human, Epigenesis, Genetic, Cell Line, Tumor, Mice, Histone Demethylases, Epithelial-Mesenchymal Transition
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