Skip to main content

Advertisement

SpringerLink
Log in

Overactivation of Ras signaling pathway in CD133+ MPNST cells

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

Abstract

Cancer stem cells (CSCs) are believed to be the regenerative pool of cells responsible for repopulating tumors. Gaining knowledge about the signaling characteristics of CSCs is important for understanding the biology of tumors and developing novel anti-cancer therapies. We have identified a subpopulation of cells positive for CD133 (a CSC marker) from human primary malignant peripheral nerve sheath tumor (MPNST) cells which were absent in non-malignant Schwann cells. CD133 was also found to be expressed in human tissue samples and mouse MPNST cells. CD133+ cells were capable of forming spheres in non-adherent/serum-free conditions. The activation levels of Ras and its downstream effectors such as ERK, JNK, PI3K, p38K, and RalA were significantly increased in this population. Moreover, the CD133+ cells showed enhanced invasiveness which was linked to the increased expression of β-Catenin and Snail, two important proteins involved in the epithelial to mesenchymal transition, and Paxilin, a focal adhesion protein. Among other important characteristics of the CD133+ population, endoplasmic reticulum stress marker IRE1α was decreased, implying the potential sensitivity of CD133+ to the accumulation of unfolded proteins. Apoptotic indicators seemed to be unchanged in CD133+ cells when compared to the wild (unsorted) cells. Finally, in order to test the possibility of targeting CD133+ MPNST cells with Ras pathway pharmacological inhibitors, we exposed these cells to an ERK inhibitor. The wild population was more sensitive to inhibition of proliferation by this inhibitor as compared with the CD133+ cells supporting previous studies observing enhanced chemoresistance of these cells.

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

Similar content being viewed by others

References

  1. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111. doi:10.1038/35102167

    Article  PubMed  CAS  Google Scholar 

  2. Bignold LP, Coghlan BL, Jersmann HP (2006) Hansemann, Boveri, chromosomes and the gametogenesis-related theories of tumours. Cell Biol Int 30:640–644. doi:10.1016/j.cellbi.2006.04.002

    Article  PubMed  CAS  Google Scholar 

  3. D’Amour KA, Gage FH (2002) Are somatic stem cells pluripotent or lineage-restricted? Nat Med 8:213–214. doi:10.1038/nm0302-213

    Article  PubMed  Google Scholar 

  4. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401. doi:10.1038/nature03128

    Article  PubMed  CAS  Google Scholar 

  5. Akhtar K, Bussen W, Scott SP (2009) Cancer stem cells—from initiation to elimination, how far have we reached? (review). Int J Oncol 34:1491–1503

    PubMed  Google Scholar 

  6. Trosko JE (2009) Review paper: cancer stem cells and cancer nonstem cells: from adult stem cells or from reprogramming of differentiated somatic cells. Vet Pathol 46:176–193. doi:10.1354/vp.46-2-176

    PubMed  CAS  Google Scholar 

  7. Pan Y, Huang X (2008) Epithelial ovarian cancer stem cells—a review. Int J Clin Exp Med 1:260–266

    PubMed  CAS  Google Scholar 

  8. Sagar J, Chaib B, Sales K, Winslet M, Seifalian A (2007) Role of stem cells in cancer therapy and cancer stem cells: a review. Cancer Cell Int 7:9. doi:10.1186/1475-2867-7-9

    Article  PubMed  Google Scholar 

  9. Spillane JB, Henderson MA (2007) Cancer stem cells: a review. ANZ J Surg 77:464–468. doi:10.1111/j.1445-2197.2007.04096.x

    Article  PubMed  Google Scholar 

  10. Costa FF, Le Blanc K, Brodin B (2007) Concise review: cancer/testis antigens, stem cells, and cancer. Stem Cells 25:707–711. doi:10.1634/stemcells.2006-0469

    Article  PubMed  CAS  Google Scholar 

  11. Mimeault M, Batra SK (2006) Concise review: recent advances on the significance of stem cells in tissue regeneration and cancer therapies. Stem Cells 24:2319–2345. doi:10.1634/stemcells.2006-0066

    Article  PubMed  CAS  Google Scholar 

  12. Meeker AK, Coffey DS (1997) Telomerase: a promising marker of biological immortality of germ, stem, and cancer cells. A review. Biochemistry 62:1323–1331

    PubMed  CAS  Google Scholar 

  13. Rudland PS, Ormerod EJ, Paterson FC (1980) Stem cells in rat mammary development and cancer: a review. J R Soc Med 73:437–442

    PubMed  CAS  Google Scholar 

  14. Polyak K, Hahn WC (2006) Roots and stems: stem cells in cancer. Nat Med 12:296–300. doi:10.1038/nm1379

    Article  PubMed  CAS  Google Scholar 

  15. Huntly BJ, Gilliland DG (2005) Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 5:311–321. doi:10.1038/nrc1592

    Article  PubMed  CAS  Google Scholar 

  16. Downward J (2003) Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3:11–22

    Article  PubMed  CAS  Google Scholar 

  17. Brannan CI, Perkins AS, Vogel KS, Ratner N, Nordlund ML, Reid SW, Buchberg AM, Jenkins NA, Parada LF, Copeland NG (1994) Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes Dev 8:1019–1029

    Article  PubMed  CAS  Google Scholar 

  18. Goldfinger LE (2008) Choose your own path: specificity in Ras GTPase signaling. Mol Biosyst 4:293–299

    Article  PubMed  CAS  Google Scholar 

  19. Rajalingam K, Schreck R, Rapp UR, Albert S (2007) Ras oncogenes and their downstream targets. Biochim Biophys Acta 1773:1177–1195

    Article  PubMed  CAS  Google Scholar 

  20. Giehl K (2005) Oncogenic Ras in tumour progression and metastasis. Biol Chem 386:193–205

    Article  PubMed  CAS  Google Scholar 

  21. Harrisingh MC, Perez-Nadales E, Parkinson DB, Malcolm DS, Mudge AW, Lloyd AC (2004) The Ras/Raf/ERK signalling pathway drives Schwann cell dedifferentiation. EMBO J 23:3061–3071

    Article  PubMed  CAS  Google Scholar 

  22. Harrisingh MC, Lloyd AC (2004) Ras/Raf/ERK signalling and NF1. Cell Cycle 3(10):1255–1258

    Google Scholar 

  23. Bollag G, Clapp DW, Shih S, Adler F, Zhang YY, Thompson P, Lange BJ, Freedman MH, McCormick F, Jacks T, Shannon K (1996) Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet 12:144–148

    Article  PubMed  CAS  Google Scholar 

  24. Hiatt KK, Ingram DA, Zhang Y, Bollag G, Clapp DW (2001) Neurofibromin GTPase-activating protein-related domains restore normal growth in Nf1−/− cells. J Biol Chem 276:7240–7245

    Article  PubMed  CAS  Google Scholar 

  25. Basu TN, Gutmann DH, Fletcher JA, Glover TW, Collins FS, Downward J (1992) Aberrant regulation of Ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Nature 356:713–715

    Article  PubMed  CAS  Google Scholar 

  26. Lakkis MM, Tennekoon GI (2000) Neurofibromatosis type 1. I. General overview. J Neurosci Res 62:755–763

    Article  PubMed  CAS  Google Scholar 

  27. Upadhyaya M, Spurlock G, Majounie E, Griffiths S, Forrester N, Baser M, Huson SM, Gareth Evans D, Ferner R (2006) The heterogeneous nature of germline mutations in NF1 patients with malignant peripheral serve sheath tumours (MPNSTs). Hum Mutat 27:716

    Article  PubMed  Google Scholar 

  28. Ferner RE (2007) Neurofibromatosis 1. Eur J Hum Genet 15:131–138

    Article  PubMed  CAS  Google Scholar 

  29. Bodempudi V, Yamoutpoor F, Pan W, Dudek AZ, Esfandyari T, Piedra M, Babovick-Vuksanovic D, Woo RA, Mautner VF, Kluwe L, Clapp DW, De Vries GH, Thomas SL, Kurtz A, Parada LF, Farassati F (2009) Ral overactivation in malignant peripheral nerve sheath tumors. Mol Cell Biol 29:3964–3974

    Article  PubMed  CAS  Google Scholar 

  30. Menon AG, Anderson KM, Riccardi VM, Chung RY, Whaley JM, Yandell DW, Farmer GE, Freiman RN, Lee JK, Li FP (1990) Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. Proc Natl Acad Sci USA 87:5435–5439

    Article  PubMed  CAS  Google Scholar 

  31. Legius E, Dierick H, Wu R, Hall BK, Marynen P, Cassiman JJ, Glover TW (1994) TP53 mutations are frequent in malignant NF1 tumors. Genes Chromosomes Cancer 10:250–255

    Article  PubMed  CAS  Google Scholar 

  32. Rey JA, Pestana A, Bello MJ (1992) Cytogenetics and molecular genetics of nervous system tumors. Oncol Res 4:321–331

    PubMed  CAS  Google Scholar 

  33. Farassati F, Yang AD, Lee PW (2001) Oncogenes in Ras signalling pathway dictate host-cell permissiveness to herpes simplex virus 1. Nat Cell Biol 3:745–750

    Article  PubMed  CAS  Google Scholar 

  34. Corbeil D, Fargeas CA, Huttner WB (2001) Rat prominin, like its mouse and human orthologues, is a pentaspan membrane glycoprotein. Biochem Biophys Res Commun 285:939–944. doi:10.1006/bbrc.2001.5271

    Article  PubMed  CAS  Google Scholar 

  35. Corbeil D, Roper K, Fargeas CA, Joester A, Huttner WB (2001) Prominin: a story of cholesterol, plasma membrane protrusions and human pathology. Traffic 2:82–91

    Article  PubMed  CAS  Google Scholar 

  36. Mehra N, Penning M, Maas J, Beerepoot LV, van Daal N, van Gils CH, Giles RH, Voest EE (2006) Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases. Clin Cancer Res 12:4859–4866. doi:10.1158/1078-0432.CCR-06-0422

    Article  PubMed  CAS  Google Scholar 

  37. Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90:5013–5021

    PubMed  CAS  Google Scholar 

  38. Salmaggi A, Boiardi A, Gelati M, Russo A, Calatozzolo C, Ciusani E, Sciacca FL, Ottolina A, Parati EA, La Porta C, Alessandri G, Marras C, Croci D, De Rossi M (2006) Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype. Glia 54:850–860. doi:10.1002/glia.20414

    Article  PubMed  Google Scholar 

  39. Monzani E, Facchetti F, Galmozzi E, Corsini E, Benetti A, Cavazzin C, Gritti A, Piccinini A, Porro D, Santinami M, Invernici G, Parati E, Alessandri G, La Porta CA (2007) Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer 43:935–946. doi:10.1016/j.ejca.2007.01.017

    Article  PubMed  CAS  Google Scholar 

  40. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110. doi:10.1038/nature05372

    Article  PubMed  Google Scholar 

  41. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951. doi:10.1158/0008-5472.CAN-05-2018

    Article  PubMed  CAS  Google Scholar 

  42. Neuzil J, Stantic M, Zobalova R, Chladova J, Wang X, Prochazka L, Dong L, Andera L, Ralph SJ (2007) Tumour-initiating cells vs. cancer ‘stem’ cells and CD133: What’s in the name? Biochem Biophys Res Commun 355:855–859. doi:10.1016/j.bbrc.2007.01.159

    Article  PubMed  CAS  Google Scholar 

  43. Hambardzumyan D, Squatrito M, Holland EC (2006) Radiation resistance and stem-like cells in brain tumors. Cancer Cell 10:454–456. doi:10.1016/j.ccr.2006.11.008

    Article  PubMed  CAS  Google Scholar 

  44. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17:165–172. doi:10.1016/j.cub.2006.11.033

    Article  PubMed  CAS  Google Scholar 

  45. Frank NY, Margaryan A, Huang Y, Schatton T, Waaga-Gasser AM, Gasser M, Sayegh MH, Sadee W, Frank MH (2005) ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res 65:4320–4333. doi:10.1158/0008-5472.CAN-04-3327

    Article  PubMed  CAS  Google Scholar 

  46. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760. doi:10.1038/nature05236

    Article  PubMed  CAS  Google Scholar 

  47. Mashour GA, Drissel SN, Frahm S, Farassati F, Martuza RL, Mautner VF, Kindler-Rohrborn A, Kurtz A (2005) Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids. Oncogene 24:2367–2374

    Article  PubMed  CAS  Google Scholar 

  48. Thomas SL, Deadwyler GD, Tang J, Stubbs EB Jr, Muir D, Hiatt KK, Clapp DW, De Vries GH (2006) Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells. Biochem Biophys Res Commun 348:971–980. doi:S0006-291X(06)01704-910.1016/j.bbrc.2006.07.159

    Article  PubMed  CAS  Google Scholar 

  49. Vogel KS, Klesse LJ, Velasco-Miguel S, Meyers K, Rushing EJ, Parada LF (1999) Mouse tumor model for neurofibromatosis type 1. Science 286:2176–2179

    Article  PubMed  CAS  Google Scholar 

  50. Bergeron JJ, Brenner MB, Thomas DY, Williams DB (1994) Calnexin: a membrane-bound chaperone of the endoplasmic reticulum. Trends Biochem Sci 19:124–128

    Article  PubMed  CAS  Google Scholar 

  51. Kohno K, Normington K, Sambrook J, Gething MJ, Mori K (1993) The promoter region of the yeast KAR2 (BiP) gene contains a regulatory domain that responds to the presence of unfolded proteins in the endoplasmic reticulum. Mol Cell Biol 13:877–890

    PubMed  CAS  Google Scholar 

  52. Ellgaard L, Ruddock LW (2005) The human protein disulphide isomerase family: substrate interactions and functional properties. EMBO Rep 6:28–32. doi:10.1038/sj.embor.7400311

    Article  PubMed  CAS  Google Scholar 

  53. Cabibbo A, Pagani M, Fabbri M, Rocchi M, Farmery MR, Bulleid NJ, Sitia R (2000) ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J Biol Chem 275:4827–4833

    Article  PubMed  CAS  Google Scholar 

  54. Cox JS, Shamu CE, Walter P (1993) Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell 73:1197–1206

    Article  PubMed  CAS  Google Scholar 

  55. Harding HP, Zhang Y, Ron D (1999) Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397:271–274. doi:10.1038/16729

    Article  PubMed  CAS  Google Scholar 

  56. Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC (1998) Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol Cell Biol 18:7499–7509

    PubMed  CAS  Google Scholar 

  57. Hancock CN, Macias A, Lee EK, Yu SY, Mackerell AD Jr, Shapiro P (2005) Identification of novel extracellular signal-regulated kinase docking domain inhibitors. J Med Chem 48:4586–4595. doi:10.1021/jm0501174

    Article  PubMed  CAS  Google Scholar 

  58. Spyra M, Kluwe L, Hagel C, Nguyen R, Panse J, Kurtz A, Mautner VF, Rabkin SD, Demestre M (2011) Cancer stem cell-like cells derived from malignant peripheral nerve sheath tumors. PLoS ONE 6:e21099. doi:10.1371/journal.pone.0021099

    Article  PubMed  CAS  Google Scholar 

  59. Farassati F, Pan W, Yamoutpour F, Henke S, Piedra M, Frahm S, Al-Tawil S, Mangrum WI, Parada LF, Rabkin SD, Martuza RL, Kurtz A (2008) Ras signaling influences permissiveness of malignant peripheral nerve sheath tumor cells to oncolytic herpes. Am J Pathol 173:1861–1872

    Article  PubMed  CAS  Google Scholar 

  60. Norman KL, Farassati F, Lee PW (2001) Oncolytic viruses and cancer therapy. Cytokine Growth Factor Rev 12:271–282

    Article  PubMed  CAS  Google Scholar 

  61. Pan W, Bodempudi V, Esfandyari T, Farassati F (2009) Utilizing Ras signaling pathway to direct selective replication of herpes simplex virus-1. PLoS ONE 4:e6514

    Article  PubMed  Google Scholar 

  62. Tabu K, Kimura T, Sasai K, Wang L, Bizen N, Nishihara H, Taga T, Tanaka S (2010) Analysis of an alternative human CD133 promoter reveals the implication of Ras/ERK pathway in tumor stem-like hallmarks. Mol Cancer 9:39. doi:10.1186/1476-4598-9-39

    Article  PubMed  Google Scholar 

  63. Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA (2000) The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2:76–83. doi:10.1038/35000025

    Article  PubMed  CAS  Google Scholar 

  64. Kato N, Shimmura S, Kawakita T, Miyashita H, Ogawa Y, Yoshida S, Higa K, Okano H, Tsubota K (2007) Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium. Invest Ophthalmol Vis Sci 48:1511–1517. doi:10.1167/iovs.06-1060

    Article  PubMed  Google Scholar 

  65. Zheng G, Lyons JG, Tan TK, Wang Y, Hsu TT, Min D, Succar L, Rangan GK, Hu M, Henderson BR, Alexander SI, Harris DC (2009) Disruption of E-cadherin by matrix metalloproteinase directly mediates epithelial-mesenchymal transition downstream of transforming growth factor-beta1 in renal tubular epithelial cells. Am J Pathol 175:580–591. doi:10.2353/ajpath.2009.080983

    Article  PubMed  CAS  Google Scholar 

  66. McGuire JK, Li Q, Parks WC (2003) Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am J Pathol 162:1831–1843

    Article  PubMed  CAS  Google Scholar 

  67. Monteiro J, Fodde R (2010) Cancer stemness and metastasis: therapeutic consequences and perspectives. Eur J Cancer 46:1198–1203. doi:10.1016/j.ejca.2010.02.030

    Article  PubMed  CAS  Google Scholar 

  68. Maheswaran S, Haber DA (2010) Circulating tumor cells: a window into cancer biology and metastasis. Curr Opin Genet Dev 20:96–99. doi:10.1016/j.gde.2009.12.002

    Article  PubMed  CAS  Google Scholar 

  69. Wang G, Yang ZQ, Zhang K (2010) Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am J Transl Res 2:65–74

    PubMed  Google Scholar 

  70. Schleicher SM, Moretti L, Varki V, Lu B (2010) Progress in the unraveling of the endoplasmic reticulum stress/autophagy pathway and cancer: implications for future therapeutic approaches. Drug Resist Updates 13:79–86. doi:10.1016/j.drup.2010.04.002

    Article  CAS  Google Scholar 

  71. Lisbona F, Hetz C (2009) Turning off the unfolded protein response: an interplay between the apoptosis machinery and ER stress signaling. Cell Cycle 8:1643–1644

    Article  PubMed  CAS  Google Scholar 

  72. Lisbona F, Rojas-Rivera D, Thielen P, Zamorano S, Todd D, Martinon F, Glavic A, Kress C, Lin JH, Walter P, Reed JC, Glimcher LH, Hetz C (2009) BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha. Mol Cell 33:679–691. doi:10.1016/j.molcel.2009.02.017

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We wish to acknowledge the efforts of the dedicated staff of the Children Tumor Foundation (CTF) in helping neurofibromatosis patients and supporting related research. We would like to express our gratitude to Dr. George H. DeVries for access to MPNST cells. In addition, we recognize Professor A. Guha for the MPNST cell-lines T530 and T532. We also wish to acknowledge Sarah Ann Martin for providing scientific editorial services for this manuscript, Fernald Stanton for assistance with microscopy, and Richard Hastings for assistance with flow cytometry.

Author information

Authors and Affiliations

  1. KUMC—Molecular Medicine Laboratory, Department of Medicine, The University of Kansas Medical Center, 3901-Rainbow Blvd, 1000 Hixon-Mail Stop: 4037, Kansas city, KS, 66160, USA

    Emma Borrego-Diaz, Kaoru Terai, Kristina Lialyte, Amanda L. Wise, Tuba Esfandyari, Fariba Behbod, Sarah Taylor & Faris Farassati

  2. University Hospital Eppendorf, Hamburg, Germany

    Victor F. Mautner & Melanie Spyra

  3. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Luis F. Parada

  4. Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, UK

    Meena Upadhyaya

Authors
  1. Emma Borrego-Diaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaoru Terai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kristina Lialyte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amanda L. Wise
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tuba Esfandyari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fariba Behbod
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Victor F. Mautner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Melanie Spyra
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sarah Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luis F. Parada
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Meena Upadhyaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Faris Farassati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Faris Farassati.

Additional information

Kaoru Terai and Kristina Lialyte have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Borrego-Diaz, E., Terai, K., Lialyte, K. et al. Overactivation of Ras signaling pathway in CD133+ MPNST cells. J Neurooncol 108, 423–434 (2012). https://doi.org/10.1007/s11060-012-0852-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-012-0852-1

Keywords

Search

Navigation