Movatterモバイル変換

[0]ホーム
URL:

Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Nature Chemistry
  • Article
  • Published:

CD44 regulates epigenetic plasticity by mediating iron endocytosis

Nature Chemistryvolume 12, pages929–938 (2020)Cite this article

Subjects

Abstract

CD44 is a transmembrane glycoprotein linked to various biological processes reliant on epigenetic plasticity, which include development, inflammation, immune responses, wound healing and cancer progression. Although it is often referred to as a cell surface marker, the functional regulatory roles of CD44 remain elusive. Here we report the discovery that CD44 mediates the endocytosis of iron-bound hyaluronates in tumorigenic cell lines, primary cancer cells and tumours. This glycan-mediated iron endocytosis mechanism is enhanced during epithelial–mesenchymal transitions, in which iron operates as a metal catalyst to demethylate repressive histone marks that govern the expression of mesenchymal genes. CD44 itself is transcriptionally regulated by nuclear iron through a positive feedback loop, which is in contrast to the negative regulation of the transferrin receptor by excess iron. Finally, we show that epigenetic plasticity can be altered by interfering with iron homeostasis using small molecules. This study reveals an alternative iron-uptake mechanism that prevails in the mesenchymal state of cells, which illuminates a central role of iron as a rate-limiting regulator of epigenetic plasticity.

This is a preview of subscription content,access via your institution

Access options

Access through your institution

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

9,800 Yen / 30 days

cancel any time

Subscription info for Japanese customers

We have a dedicated website for our Japanese customers. Please go tonatureasia.com to subscribe to this journal.

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

￥ 4,980

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: CD44 mediates Hyal-dependent iron endocytosis.
Fig. 2: CD44-mediated iron endocytosis prevails in the mesenchymal state of cells.
Fig. 3: EMT is characterized by a redox signature that implicates iron.
Fig. 4: Nuclear iron is a rate-limiting regulator of epigenetic plasticity.
Fig. 5: Targeting iron homeostasis interferes with the maintenance of mesenchymal cells.
Fig. 6: Reciprocal endocytic–epigenetic regulation that involves iron.

Similar content being viewed by others

Data availability

All data are available in the manuscript or theSupplementary Information. Mass spectrometry data have been deposited at the ProteomeXchange Consortium (PRIDE Archive) with identifiersPXD011447 andPXD012862. ChIP-seq and RNA-seq data are available on the National Center for Biotechnology Information website with accession referenceGSE121664.Source data are provided with this paper.

Code availability

Code employed for ChIP-seq and RNA-seq data analyses are available on Github athttps://github.com/nservant/EMTiron.

References

  1. Ponta, H., Sherman, L. & Herrlich, P. A. CD44: from adhesion molecules to signalling regulators.Nat. Rev. Mol. Cell Biol.4, 33–45 (2003).

    Article CAS PubMed  Google Scholar 

  2. Zöller, M. CD44: can a cancer-initiating cell profit from an abundantly expressed molecule?Nat. Rev. Cancer11, 254–267 (2011).

    Article PubMed CAS  Google Scholar 

  3. Nieto, M. A., Huang, R. Y., Jackson, R. A. & Thiery, J. P. EMT: 2016.Cell166, 21–45 (2016).

    Article CAS PubMed  Google Scholar 

  4. Brabletz, T., Kalluri, R., Nieto, M. A. & Weinberg, R. A. EMT in cancer.Nat. Rev. Cancer18, 128–134 (2018).

    Article CAS PubMed  Google Scholar 

  5. Pastushenko, I. et al. Identification of the tumour transition states occurring during EMT.Nature556, 463–468 (2018).

    Article CAS PubMed  Google Scholar 

  6. Günthert, U. et al. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells.Cell65, 13–24 (1991).

    Article PubMed  Google Scholar 

  7. Aruffo, A., Stamenkovic, I., Melnick, M., Underhill, C. B. & Seed, B. CD44 is the principal cell surface receptor for hyaluronate.Cell61, 1303–1313 (1990).

    Article CAS PubMed  Google Scholar 

  8. Hua, Q., Knudson, C. B. & Knudson, W. Internalization of hyaluronan by chondrocytes occurs via receptor-mediated endocytosis.J. Cell Sci.106, 365–375 (1993).

    Article CAS PubMed  Google Scholar 

  9. Bartolazzi, A., Peach, R., Aruffo, A. & Stamenkovic, I. Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development.J. Exp. Med.180, 53–66 (1994).

    Article CAS PubMed  Google Scholar 

  10. Zoltan-Jones, A., Huang, L., Ghatak, S. & Toole, B. P. Elevated hyaluronan production induces mesenchymal and transformed properties in epithelial cells.J. Biol. Chem.278, 45801–45810 (2003).

    Article CAS PubMed  Google Scholar 

  11. Toole, B. P. Hyaluronan: from extracellular glue to pericellular cue.Nat. Rev. Cancer4, 528–539 (2004).

    Article CAS PubMed  Google Scholar 

  12. Mercê, A. L., Marques Carrera, L. C., Santos Romanholi, L. K. & Lobo Recio, M. A. Aqueous and solid complexes of iron(iii) with hyaluronic acid. Potentiometric titrations and infrared spectroscopy studies.J. Inorg. Biochem.89, 212–218 (2002).

    Article PubMed  Google Scholar 

  13. Torti, S. V. & Torti, F. M. Iron and cancer: more ore to be mined.Nat. Rev. Cancer13, 342–355 (2013).

    Article CAS PubMed PubMed Central  Google Scholar 

  14. Schonberg, D. L. et al. Preferential iron trafficking characterizes glioblastoma stem-like cells.Cancer Cell28, 441–455 (2015).

    Article CAS PubMed PubMed Central  Google Scholar 

  15. Mai, T. T. et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes.Nat. Chem.9, 1025–1033 (2017).

    Article CAS PubMed PubMed Central  Google Scholar 

  16. Basuli, D. et al. Iron addiction: a novel therapeutic target in ovarian cancer.Oncogene36, 4089–4099 (2017).

    Article CAS PubMed PubMed Central  Google Scholar 

  17. Viswanathan, V. S. et al. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway.Nature547, 453–457 (2017).

    Article CAS PubMed PubMed Central  Google Scholar 

  18. Hangauer, M. J. et al. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition.Nature551, 247–250 (2017).

    Article CAS PubMed PubMed Central  Google Scholar 

  19. Morel, A. P. et al. Generation of breast cancer stem cells through epithelial–mesenchymal transition.PLoS One3, e2888 (2008).

    Article PubMed PubMed Central CAS  Google Scholar 

  20. Niwa, M., Hirayama, T., Okuda, K. & Nagasawa, H. A new class of high-contrast Fe(ii) selective fluorescent probes based on spirocyclized scaffolds for visualization of intracellular labile iron delivered by transferrin.Org. Biomol. Chem.12, 6590–6597 (2014).

    Article CAS PubMed  Google Scholar 

  21. Guerquin-Kern, J. L., Wu, T. D., Quintana, C. & Croisy, A. Progress in analytical imaging of the cell by dynamic secondary ion mass spectrometry (SIMS microscopy).Biochim. Biophys. Acta1724, 228–238 (2005).

    Article CAS PubMed  Google Scholar 

  22. Stuelten, C. H. et al. Complex display of putative tumor stem cell markers in the NCI60 tumor cell line panel.Stem Cells28, 649–660 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  23. Pantopoulos, K., Porwal, S. K., Tartakoff, A. & Devireddy, L. Mechanisms of mammalian iron homeostasis.Biochemistry51, 5705–5724 (2012).

    Article CAS PubMed  Google Scholar 

  24. Muckenthaler, M. U., Rivella, S., Hentze, M. W. & Galy, B. A red carpet for iron metabolism.Cell168, 344–361 (2017).

    Article CAS PubMed PubMed Central  Google Scholar 

  25. Chuang, C. H. et al. Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis.Nat. Med.23, 291–300 (2017).

    Article CAS PubMed PubMed Central  Google Scholar 

  26. Bendris, N. et al. SNX9 promotes metastasis by enhancing cancer cell invasion via differential regulation of RhoGTPases.Mol. Biol. Cell27, 1409–1419 (2016).

    Article CAS PubMed Central  Google Scholar 

  27. Feng, W., Yonezawa, M., Ye, J., Jenuwein, T. & Grummt, I. PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation.Nat. Struct. Mol. Biol.17, 445–450 (2010).

    Article CAS PubMed  Google Scholar 

  28. Fortschegger, K. et al. PHF8 targets histone methylation and RNA polymerase II to activate transcription.Mol. Cell. Biol.30, 3286–3298 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  29. Liu, W. et al. PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.Nature466, 508–512 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  30. Qi, H. H. et al. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development.Nature466, 503–507 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  31. Shao, P. et al. Histone demethylase PHF8 promotes epithelial to mesenchymal transition and breast tumorigenesis.Nucleic Acids Res.45, 1687–1702 (2017).

    Article CAS PubMed  Google Scholar 

  32. Carey, B. W., Finley, L. W., Cross, J. R., Allis, C. D. & Thompson, C. B. Intracellular alpha-ketoglutarate maintains the pluripotency of embryonic stem cells.Nature518, 413–416 (2015).

    Article CAS PubMed  Google Scholar 

  33. Bullock, G. C. et al. Iron control of erythroid development by a novel aconitase-associated regulatory pathway.Blood116, 97–108 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  34. Li, X., Egervari, G., Wang, Y., Berger, S. L. & Lu, Z. Regulation of chromatin and gene expression by metabolic enzymes and metabolites.Nat. Rev. Mol. Cell Biol.19, 563–578 (2018).

    Article CAS PubMed PubMed Central  Google Scholar 

  35. Smith, A. G., Carthew, P., Francis, J. E., Edwards, R. E. & Dinsdale, D. Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload.Hepatology12, 1399–1405 (1990).

    Article CAS PubMed  Google Scholar 

  36. Yu, L. et al. Structural insights into a novel histone demethylase PHF8.Cell Res.20, 166–173 (2010).

    Article CAS PubMed  Google Scholar 

  37. McDonald, O. G., Wu, H., Timp, W., Doi, A. & Feinberg, A. P. Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition.Nat. Struct. Mol. Biol.18, 867–874 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  38. Zhao, Q. Y. et al. Global histone modification profiling reveals the epigenomic dynamics during malignant transformation in a four-stage breast cancer model.Clin. Epigenetics8, 34 (2016).

    Article PubMed PubMed Central CAS  Google Scholar 

  39. McDonald, O. G. et al. Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis.Nat. Genet.49, 367–376 (2017).

    Article CAS PubMed PubMed Central  Google Scholar 

  40. Gerry, C. J. & Schreiber, S. L. Chemical probes and drug leads from advances in synthetic planning and methodology.Nat. Rev. Drug Discov.17, 333–352 (2018).

    Article CAS PubMed PubMed Central  Google Scholar 

  41. Cañeque, T., Müller, S. & Rodriguez, R. Visualizing biologically active small molecules in cells using click chemistry.Nat. Rev. Chem.2, 202–215 (2018).

    Article  Google Scholar 

  42. Müller, S. et al. Metformin reveals a mitochondrial copper addiction of mesenchymal cancer cells.PLoS One13, e0206764 (2018).

    Article PubMed PubMed Central CAS  Google Scholar 

  43. Janzer, A. et al. Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells.Proc. Natl Acad. Sci. USA111, 10574–10579 (2014).

    Article CAS PubMed PubMed Central  Google Scholar 

  44. Zilka, O. et al. On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death.ACS Cent. Sci.3, 232–243 (2017).

    Article CAS PubMed PubMed Central  Google Scholar 

  45. Conrad, M. & Pratt, D. A. The chemical basis of ferroptosis.Nat. Chem. Biol.15, 1137–1147 (2019).

    Article CAS PubMed  Google Scholar 

  46. Flavahan, W. A., Gaskell, E. & Bernstein, B. E. Epigenetic plasticity and the hallmarks of cancer.Science357, eaal2380 (2017).

    Article PubMed PubMed Central CAS  Google Scholar 

  47. Tian, X. et al. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat.Nature499, 346–349 (2013).

    Article CAS PubMed PubMed Central  Google Scholar 

  48. Gerken, T. et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.Science318, 1469–1472 (2007).

    Article CAS PubMed PubMed Central  Google Scholar 

  49. Jia, G. et al.N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.Nat. Chem. Biol.7, 885–887 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  50. Greer, E. L. & Shi, Y. Histone methylation: a dynamic mark in health, disease and inheritance.Nat. Rev. Genet.13, 343–357 (2012).

    Article CAS PubMed PubMed Central  Google Scholar 

  51. Tsai, Y. P. et al. TET1 regulates hypoxia-induced epithelial–mesenchymal transition by acting as a co-activator.Genome Biol.15, 513 (2014).

    Article PubMed PubMed Central CAS  Google Scholar 

Download references

Acknowledgements

We thank A. Puisieux, C. Hivroz and S. Dogniaux for providing us with HMLER and primary human T cells, the PICT-IBiSA@Pasteur Imaging Facility of Institut Curie, a member of the France-BioImaging national research infrastructure for the use of microscopes and SIMS, C. Gaillet for assistance with NMR spectroscopy, J.-L. Guerquin-Kern for assistance with SIMS sample preparation, the ICP-MS platform at the Institut de Physique du Globe de Paris, G. Arras for assistance with mass spectrometry data analysis, S. Durand and G. Kroemer for providing access to the metabolomics platform and P. Legoix for NGS sample preparation. The R.R. research group is funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 647973), the Fondation Charles Defforey-Institut de France and Ligue Contre le Cancer (Equipe Labellisée). R.R. and D.L. are supported by Region IdF for NMR and MS infrastructures. The Institut de Physique du Globe de Paris is supported by the IPGP multidisciplinary program PARI and Paris–Region IdF (SESAME grant agreement no. 12015908). High-throughput sequencing was performed by the ICGex NGS platform of Institut Curie, supported by ANR-10-EQPX-03 (Equipex), ANR-10-INBS-09-08 (France Génomique Consortium) from the Agence Nationale de la Recherche (Investissements d’Avenir program) and by the Cancéropole IdF and the SiRIC-Curie program—SiRIC Grant (INCa-DGOS-4654).

Author information

Author notes

  1. These authors contributed equally: Sebastian Müller, Fabien Sindikubwabo.

Authors and Affiliations

  1. Institut Curie, Paris, France

    Sebastian Müller, Fabien Sindikubwabo, Tatiana Cañeque, Anne Lafon, Antoine Versini, Bérangère Lombard, Damarys Loew, Ting-Di Wu, Adeline Durand, Céline Vallot, Sylvain Baulande, Nicolas Servant & Raphaël Rodriguez

  2. PSL Université, Paris, France

    Sebastian Müller, Fabien Sindikubwabo, Tatiana Cañeque, Anne Lafon, Antoine Versini, Bérangère Lombard, Damarys Loew, Ting-Di Wu, Adeline Durand, Céline Vallot, Sylvain Baulande & Raphaël Rodriguez

  3. Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France

    Sebastian Müller, Fabien Sindikubwabo, Tatiana Cañeque, Anne Lafon, Antoine Versini & Raphaël Rodriguez

  4. Proteomics Mass Spectrometry Laboratory, Paris, France

    Bérangère Lombard & Damarys Loew

  5. Paris-Sud Université, Paris-Saclay Université, CNRS UMR 9187, INSERM U1196, Paris, France

    Ting-Di Wu

  6. Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France

    Christophe Ginestier & Emmanuelle Charafe-Jauffret

  7. Epithelial Stem Cells and Cancer Laboratory, CNRS UMR 10668, INSERM U1068, Marseille, France

    Christophe Ginestier & Emmanuelle Charafe-Jauffret

  8. Translational Research Department, CNRS UMR 3244, Paris, France

    Adeline Durand & Céline Vallot

  9. Institut Curie Genomics of Excellence Platform, Paris, France

    Sylvain Baulande

  10. CBIO-Centre for Computational Biology, INSERM U900, Mines ParisTech, Paris, France

    Nicolas Servant

Authors
  1. Sebastian Müller
  2. Fabien Sindikubwabo
  3. Tatiana Cañeque
  4. Anne Lafon
  5. Antoine Versini
  6. Bérangère Lombard
  7. Damarys Loew
  8. Ting-Di Wu
  9. Christophe Ginestier
  10. Emmanuelle Charafe-Jauffret
  11. Adeline Durand
  12. Céline Vallot
  13. Sylvain Baulande
  14. Nicolas Servant
  15. Raphaël Rodriguez

Contributions

R.R. conceptualized the study and directed the research. R.R., S.M. and F.S. designed the experiments. T.C. performed NMR spectroscopy and synthesized the clickable iron chelators. A.V. synthesized the iron(ii)-specific fluorescent probes. S.M. produced knock out cell lines and performed the experiments in relation to iron endocytosis, which included western blotting, cell imaging, RNA interference, flow cytometry and ICP-MS. T.-D.W. performed SIMS imaging. A.L. performed RT-qPCR and subcellular fractionation experiments. F.S. prepared the samples for quantitative proteomics, metabolomics and next generation sequencing. B.L. and D.L. carried out quantitative proteomics. E.C.-J. and C.G. provided tumour samples and performed cell sorting. A.D., C.V. and S.B. provided assistance with the NGS library preparation. N.S. performed bioinformatics analysis. R.R., S.M. and F.S. interpreted the data and wrote the article.

Corresponding author

Correspondence toRaphaël Rodriguez.

Ethics declarations

Competing interests

R.R. is a founder, shareholder and serves on the scientific advisory board of SideROS.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 CD44-mediates iron endocytosis in distinct cell lines and primary cells.

a, Fluorescence microscopy of RhoNox-M-positive vesicles colocalizing with internalized Hyal-FITC or TF-647 (left panels). Scale bars, 10 μm.n = 3 biologically independent experiments for MDA-MB-468, U2OS and HT1080 cell lines andn = 1 for primary cancer cells and the LNCaP cell line. Flow cytometry of CD44 (right panels).b, Fluorescence microscopy of RhoNox-M-positive vesicles colocalizing with internalized Hyal-FITC in primary human T cells (left panel). Scale bar, 2 μm.n = 3 biologically independent experiments. Flow cytometry of CD44 (right panel). Bars and error bars, mean values ± s.d.

Extended Data Fig. 2 CD44-mediated iron uptake is Hyal-dependent in distinct cell lines and primary cells.

a, Flow cytometry of RhoNox-M fluorescence in HMLERCD44 andTFRC ko clones and a MCF7CD44 ko clone treated with Hyal.b, Flow cytometry of RhoNox-M fluorescence in primary cancer cells and primary T cells treated with Hyal.n = 1.c, Flow cytometry of RhoNox-M fluorescence in MDA-MB-468 cells treated with Hyal of varying molecular mass.d, ande, Flow cytometry of RhoNox-M in MDA-MB-468, primary lung CTC, HMLER CD44high and MCF7 cells treated with Hyal, hyaluronidase or blocking antibodies.n = 1. HMM Hyal (0.6-1 MDa) was used ina,b,d. Data representative ofn = 3 biologically independent experiments fora andc.

Extended Data Fig. 3 CD44-mediated iron endocytosis prevails in the mesenchymal state of cells.

a, Time course flow cytometry of CD44 and TfR1 at plasma membrane of MCF7 and HMLER CD44low cells treated with OSM or TGF-β as indicated. Data representative ofn = 3 biologically independent experiments.b, Fluorescence microscopy of RhoNox-M-positive vesicles colocalizing with internalized Hyal-FITC or TF-647 in cells treated as indicated for 72 h. Scale bars, 10 μm.n = 3 biologically independent experiments for MCF7 cells andn = 1 for primary cells. Bars and error bars, mean values ± s.d. Unpairedt-tests, two-sided.

Extended Data Fig. 4 Quantitative analysis of proteins and metabolites in cells undergoing EMT.

a, Gene Ontology-term enrichment heatmap of proteins ranked by molecular function illustrating a bias towards proteins with oxidoreductase activity being increased in the mesenchymal cell state.n = 3 biologically independent experiments. Statistical analysis, Material and Methods.b, Western blots of selected proteins. Data representative ofn = 3 biologically independent experiments.c, Heatmap of metabolites in cells treated with EGF for 60 h.n = 4 technical replicates. MDA-MB-468 cells throughout the figure and treated with EGF for 72 h unless stated otherwise.

Extended Data Fig. 5 Genome-wide analysis of histone marks in cells undergoing EMT.

a, H3K9me2 ChIP-seq profiles for selected genes.n = 3 biologically independent experiments.b, ChIP-qPCR of selected genes.n = 2 biologically independent experiments.c−e, ChIP-seq profiles of H3K4me3, H3K27me3 and H3K9me3 for selected genes.n = 2 biologically independent experiments. MDA-MB-468 cells were used throughout the figure and treated with EGF for 72 h.

Extended Data Fig. 6 Pharmacological targeting of iron-regulated processes.

a, Western blots of H3K9me2 in cells co-treated with OSM and DFO or TGF-β and DFO as indicated.n = 1 for primary cells.b, Western blots of proteins whose genes are regulated by H3K9me2 in cells co-treated with OSM and DFO or TGF-β and DFO as indicated.n = 1 for primary cells.c, Molecular structure of clickable deferasirox (cDFX) (left), fluorescence microscopy of labelled cDFX and the mitochondrial component Cytc (right). Scale bar, 10 μm.d, αKG quantification assay of MDA-MB-468 cells co-treated with EGF and deferasirox (DFX).n = 3 technical replicates.e, Western blots of CD44 and H3K9me2 in MDA-MB-468 cells co-treated with EGF and DFX. Data representative ofn = 3 biologically independent experiments throughout the figure unless stated otherwise. Bars and error bars, mean values ± s.d.

Supplementary information

Supplementary Information

Materials and Methods, Supplementary References, Table 5 and original western blots.

Supplementary Table 1

Quantitative label-free proteomics.

Supplementary Table 2

Quantitative metabolomics.

Supplementary Table 3

Quantitative mass spectrometry analysis of histone marks.

Supplementary Table 4

ChIP-seq and RNA-seq analyses.

Source data

Source Data Fig. 1

Statistical Source Data.

Source Data Fig. 1

Unprocessed western blots.

Source Data Fig. 2

Statistical Source Data.

Source Data Fig. 2

Unprocessed western blots.

Source Data Fig. 3

Statistical Source Data.

Source Data Fig. 4

Unprocessed western blots.

Source Data Fig. 5

Statistical Source Data.

Source Data Fig. 5

Unprocessed western blots.

Source Data Extended Fig. 3

Statistical Source Data.

Source Data Extended Fig. 4

Unprocessed western blots.

Source Data Extended Fig. 6

Statistical Source Data

Source Data Extended Fig. 6

Unprocessed western blots.

Rights and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Müller, S., Sindikubwabo, F., Cañeque, T.et al. CD44 regulates epigenetic plasticity by mediating iron endocytosis.Nat. Chem.12, 929–938 (2020). https://doi.org/10.1038/s41557-020-0513-5

Download citation

This article is cited by

Access through your institution
Buy or subscribe

Advertisement

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for theNature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly.Sign up for Nature Briefing: Cancer
[8]ページ先頭
©2009-2026 Movatter.jp