Skip to main content

Advertisement

SpringerLink
Log in

ZEB1 expression is increased in IDH1-mutant lower-grade gliomas

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Transcription factors that induce epithelial-mesenchymal transition (EMT) promote invasion, chemoresistance and a stem-cell phenotype in epithelial tumors, but their roles in central nervous system tumors are not well-understood. We hypothesized these transcription factors have a functional impact in grades II–III gliomas. Using the National Cancer Institute (NCI) Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) data, we determined the impact of EMT-promoting transcription factors (EMT-TFs) on overall survival in grades II–III gliomas, compared their expression across common genetic subtypes and subsequently validated these findings in a set of 31 tumors using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. Increased expression of the gene coding for the transcriptional repressor Zinc Finger E box-binding Homeobox 1 (ZEB1) was associated with a significant increase in overall survival (OS) on Kaplan–Meier analysis. Genetic subtype analysis revealed that ZEB1 expression was relatively increased in IDH1/2-mutant gliomas, and IDH1/2-mutant gliomas expressed significantly lower levels of many ZEB1 transcriptional targets. Similarly, IDH1/2-mutant tumors expressed significantly higher levels of targets of microRNA 200C (MIR200C), a key regulator of ZEB1. In a validation study, ZEB1 mRNA was significantly increased in IDH1-mutant grades II–III gliomas, and ZEB1 protein expression was more pronounced in these tumors. Our findings demonstrate a novel relationship between IDH1/2 mutations and expression of ZEB1 and its transcriptional targets. Therapy targeting ZEB1-associated pathways may represent a novel therapeutic avenue for this class of tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507

    Article  CAS  PubMed  Google Scholar 

  2. Verhaak RG, Cooper LA, Salama SS, Aldape K, Yung WA, Brat DJ (2014) Comprehensive and integrative genomic characterization of diffuse lower grade gliomas. Cancer Res 74(19):936

    Article  Google Scholar 

  3. Brat DJ, TCGA Lower Grade Gliomas Analysis Working Group (2014) Integrative genomic characterization of lower grade gliomas. Neuro-oncology 16(suppl 3):iii3

    Article  Google Scholar 

  4. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M et al (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498

    Article  Google Scholar 

  5. Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV et al (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372:2499–2508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, zur Hausen A et al (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 11:1487–1495

    Article  CAS  PubMed  Google Scholar 

  12. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601

    Article  CAS  PubMed  Google Scholar 

  13. Edwards LA, Woolard K, Son MJ, Li A, Lee J, Ene C, Mantey SA, Maric D, Song H, Belova G et al (2011) Effect of brain- and tumor-derived connective tissue growth factor on glioma invasion. J Natl Cancer Inst 103:1162–1178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Elias MC, Tozer KR, Silber JR, Mikheeva S, Deng M, Morrison RS, Manning TC, Silbergeld DL, Glackin CA, Reh TA et al (2005) TWIST is expressed in human gliomas and promotes invasion. Neoplasia 7:824–837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Han SP, Kim JH, Han ME, Sim HE, Kim KS, Yoon S, Baek SY, Kim BS, Oh SO (2011) SNAI1 is involved in the proliferation and migration of glioblastoma cells. Cell Mol Neurobiol 31:489–496

    Article  CAS  PubMed  Google Scholar 

  16. Kahlert U, Suwala A, Raabe E, Siebzehnrubl F, Suarez M, Orr B, Bar E, Maciaczyk J, Eberhart C (2014) ZEB1 Promotes invasion in human fetal neural stem cells and hypoxic glioma neurospheres. Brain Pathol 25(6):724–732

    Article  Google Scholar 

  17. Siebzehnrubl FA, Silver DJ, Tugertimur B, Deleyrolle LP, Siebzehnrubl D, Sarkisian MR, Devers KG, Yachnis AT, Kupper MD, Neal D et al (2013) The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance. EMBO Mol Med 5:1196–1212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liao H, Bai Y, Qiu S, Zheng L, Huang L, Liu T, Wang X, Liu Y, Xu N, Yan X et al (2015) MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2. Oncotarget 6:8914–8928

    Article  PubMed  PubMed Central  Google Scholar 

  19. Qi S, Song Y, Peng Y, Wang H, Long H, Yu X, Li Z, Fang L, Wu A, Luo W et al (2012) ZEB2 mediates multiple pathways regulating cell proliferation, migration, invasion, and apoptosis in glioma. PLoS One 7:e38842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Xia M, Hu M, Wang J, Xu Y, Chen X, Ma Y, Su L (2010) Identification of the role of Smad interacting protein 1 (SIP1) in glioma. J Neurooncol 97:225–232

    Article  CAS  PubMed  Google Scholar 

  21. Yang HW, Menon LG, Black PM, Carroll RS, Johnson MD (2010) SNAI2/Slug promotes growth and invasion in human gliomas. BMC Cancer 10:301

    Article  PubMed  PubMed Central  Google Scholar 

  22. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM (2004) ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 6:1–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Madhavan S, Zenklusen JC, Kotliarov Y, Sahni H, Fine HA, Buetow K (2009) Rembrandt: helping personalized medicine become a reality through integrative translational research. Mol Cancer Res 7:157–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E et al (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404

    Article  PubMed  Google Scholar 

  25. Bredel M, Bredel C, Juric D, Harsh GR, Vogel H, Recht LD, Sikic BI (2005) Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. Cancer Res 65:8679–8689

    Article  CAS  PubMed  Google Scholar 

  26. French PJ, Swagemakers SM, Nagel JH, Kouwenhoven MC, Brouwer E, van der Spek P, Luider, Kros JM, van den Bent MJ, Sillevis Smitt PA (2005) Gene expression profiles associated with treatment response in oligodendrogliomas. Cancer Res 65:11335–11344

    Article  CAS  PubMed  Google Scholar 

  27. Liang Y, Diehn M, Watson N, Bollen AW, Aldape KD, Nicholas MK, Lamborn KR, Berger MS, Botstein D, Brown PO et al (2005) Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc Natl Acad Sci USA 102:5814–5819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shai R, Shi T, Kremen TJ, Horvath S, Liau LM, Cloughesy TF, Mischel PS, Nelson SF (2003) Gene expression profiling identifies molecular subtypes of gliomas. Oncogene 22:4918–4923

    Article  CAS  PubMed  Google Scholar 

  29. Sun L, Hui AM, Su Q, Vortmeyer A, Kotliarov Y, Pastorino S, Passaniti A, Menon J, Walling J, Bailey R et al (2006) Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell 9:287–300

    Article  CAS  PubMed  Google Scholar 

  30. Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA, Fontebasso AM, Fleming A, Hadjadj D, Schwartzentruber J, Majewski J et al (2012) Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol (Berl) 124:615–625

    Article  CAS  Google Scholar 

  32. Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH, Rodriguez FJ, Cahill DP, McLendon R, Riggins G et al (2011) Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 333:1453–1455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sahm F, Koelsche C, Meyer J, Pusch S, Lindenberg K, Mueller W, Herold-Mende C, von Deimling A, Hartmann C (2012) CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas. Acta Neuropathol (Berl) 123:853–860

    Article  CAS  Google Scholar 

  34. Grassian AR, Lin F, Barrett R, Liu Y, Jiang W, Korpal M, Astley H, Gitterman D, Henley T, Howes R et al (2012) Isocitrate dehydrogenase (IDH) mutations promote a reversible ZEB1/microRNA (miR)-200-dependent epithelial-mesenchymal transition (EMT). J Biol Chem 287:42180–42194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Aigner K, Dampier B, Descovich L, Mikula M, Sultan A, Schreiber M, Mikulits W, Brabletz T, Strand D, Obrist P et al (2007) The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Oncogene 26:6979–6988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu Y, Sanchez-Tillo E, Lu X, Huang L, Clem B, Telang S, Jenson AB, Cuatrecasas M, Chesney J, Postigo A et al (2013) Sequential inductions of the ZEB1 transcription factor caused by mutation of Rb and then Ras proteins are required for tumor initiation and progression. J Biol Chem 288:11572–11580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liu Y, Sanchez-Tillo E, Lu X, Huang L, Clem B, Telang S, Jenson AB, Cuatrecasas M, Chesney J, Postigo A et al (2014) The ZEB1 transcription factor acts in a negative feedback loop with miR200 downstream of Ras and Rb1 to regulate Bmi1 expression. J Biol Chem 289:4116–4125

    Article  CAS  PubMed  Google Scholar 

  38. Chaffer CL, Marjanovic ND, Lee T, Bell G, Kleer CG, Reinhardt F, D’Alessio AC, Young RA, Weinberg RA (2013) Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 154:61–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Liu Y, Lu X, Huang L, Wang W, Jiang G, Dean KC, Clem B, Telang S, Jenson AB, Cuatrecasas M et al (2014) Different thresholds of ZEB1 are required for Ras-mediated tumour initiation and metastasis. Nature Commun 5:5660

    Article  Google Scholar 

  40. Serna E, Lopez-Gines C, Monleon D, Munoz-Hidalgo L, Callaghan RC, Gil-Benso R, Martinetto H, Gregori-Romero A, Gonzalez-Darder J, Cerda-Nicolas M (2014) Correlation between EGFR amplification and the expression of microRNA-200c in primary glioblastoma multiforme. PLoS One 9:e102927

    Article  PubMed  PubMed Central  Google Scholar 

  41. Joseph JV, Conroy S, Tomar T, Eggens-Meijer E, Bhat K, Copray S, Walenkamp AM, Boddeke E, Balasubramanyian V, Wagemakers M et al (2014) TGF-beta is an inducer of ZEB1-dependent mesenchymal transdifferentiation in glioblastoma that is associated with tumor invasion. Cell Death Dis 5:e1443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sanchez-Tillo E, de Barrios O, Siles L, Cuatrecasas M, Castells A, Postigo A (2011) Beta-catenin/TCF4 complex induces the epithelial-to-mesenchymal transition (EMT)-activator ZEB1 to regulate tumor invasiveness. Proc Natl Acad Sci USA 108:19204–19209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wu K, Fan J, Zhang L, Ning Z, Zeng J, Zhou J, Li L, Chen Y, Zhang T, Wang X et al (2012) PI3K/Akt to GSK3beta/beta-catenin signaling cascade coordinates cell colonization for bladder cancer bone metastasis through regulating ZEB1 transcription. Cell Signal 24:2273–2282

    Article  CAS  PubMed  Google Scholar 

  44. Sun X, Jiao X, Pestell TG, Fan C, Qin S, Mirabelli E, Ren H, Pestell RG (2014) MicroRNAs and cancer stem cells: the sword and the shield. Oncogene 33:4967–4977

    Article  CAS  PubMed  Google Scholar 

  45. Ma X, Yoshimoto K, Guan Y, Hata N, Mizoguchi M, Sagata N, Murata H, Kuga D, Amano T, Nakamizo A et al (2012) Associations between microRNA expression and mesenchymal marker gene expression in glioblastoma. Neuro Oncol 14:1153–1162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE et al (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:225–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A et al (2012) IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483:474–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT et al (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 19:17–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C, Cowley GS, Root DE, Ebert BL, Kaelin WG Jr (2013) (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 339:1621–1625

    Article  CAS  PubMed  Google Scholar 

  51. Yen G, Croci A, Dowling A, Zhang S, Zoeller RT, Darling DS (2001) Developmental and functional evidence of a role for Zfhep in neural cell development. Brain Res Mol Brain Res 96:59–67

    Article  CAS  PubMed  Google Scholar 

  52. Bui T, Sequeira J, Wen TC, Sola A, Higashi Y, Kondoh H, Genetta T (2009) ZEB1 links p63 and p73 in a novel neuronal survival pathway rapidly induced in response to cortical ischemia. PLoS One 4:e4373

    Article  PubMed  PubMed Central  Google Scholar 

  53. Sabourin JC, Ackema KB, Ohayon D, Guichet PO, Perrin FE, Garces A, Ripoll C, Charite J, Simonneau L, Kettenmann H et al (2009) A mesenchymal-like ZEB1(+) niche harbors dorsal radial glial fibrillary acidic protein-positive stem cells in the spinal cord. Stem Cells 27:2722–2733

    Article  CAS  PubMed  Google Scholar 

  54. Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y et al (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science 324:261–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Koivunen P, Lee S, Duncan CG, Lopez G, Lu G, Ramkissoon S, Losman JA, Joensuu P, Bergmann U, Gross S et al (2012) Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 483:484–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bralten LB, Kloosterhof NK, Balvers R, Sacchetti A, Lapre L, Lamfers M, Leenstra S, de Jonge H, Kros JM, Jansen EE et al (2011) IDH1 R132H decreases proliferation of glioma cell lines in vitro and in vivo. Ann Neurol 69:455–463

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Ms. Barbara Ikejiri for her extensive assistance in the preparation of materials used in experiments conducted in this study. The authors also wish to thank Dr. Lynn Young of the NIH Library Bioinformatics Support Program for her guidance in the gene expression analyses performed in this study. This research was supported by the Intramural Research Program at the National Institute of Neurological Disorders and Stroke and the National Institutes of Health (NIH) Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer, Inc., The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs. Joel S. Marcus and the Howard Hughes Medical Institute, as well as other private donors. Funding sources had no role in study design; data collection, analysis or interpretation; writing of the manuscript; or decision to submit this material for publication.

Funding

This research was supported by the Intramural Research Program at the National Institute of Neurological Disorders and Stroke and the National Institutes of Health Medical Research Scholars Program.

Author information

Authors and Affiliations

  1. Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, 9000 Rockville Pike, Building 10 Room 3D17, Bethesda, MD, 20892, USA

    Cody L. Nesvick, Chao Zhang, Nancy A. Edwards, Blake K. Montgomery, Michaela Lee, Chunzhang Yang, Herui Wang, Dongwang Zhu, John D. Heiss, Marsha J. Merrill, Abhik Ray-Chaudhury & Zhengping Zhuang

  2. Department of Neurologic Surgery, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA

    Cody L. Nesvick

  3. Department of Orthopaedic Surgery, Stanford University, 450 Broadway Street, Pavilion C, 4th Floor, Redwood City, CA, 94063, USA

    Blake K. Montgomery

  4. Department of Neurological Surgery, The George Washington University, 2150 Pennsylvania Avenue NW, Suite 7-420, Washington, DC, 20037, USA

    Michaela Lee

  5. Neuro-Oncology Branch, National Cancer Institute, Building 37, Room 1142E, Bethesda, MD, 20892, USA

    Chunzhang Yang

Authors
  1. Cody L. Nesvick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nancy A. Edwards
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Blake K. Montgomery
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michaela Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chunzhang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Herui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dongwang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. John D. Heiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marsha J. Merrill
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Abhik Ray-Chaudhury
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Zhengping Zhuang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Cody L. Nesvick or Zhengping Zhuang.

Ethics declarations

Conflict of interest

The authors have no known conflicts of interest to declare.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 237 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nesvick, C.L., Zhang, C., Edwards, N.A. et al. ZEB1 expression is increased in IDH1-mutant lower-grade gliomas. J Neurooncol 130, 111–122 (2016). https://doi.org/10.1007/s11060-016-2240-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-016-2240-8

Keywords

Search

Navigation