Skip to main content
SpringerLink
Log in

Mitogen-activated protein (MAP) kinase Roles in Paediatric Brain Tumor “Medulloblastoma”

  • Chapter
  • First Online:
Role of Signaling Pathways in Brain Tumorigenesis

  • 79 Accesses

Abstract

Mitogen-activated protein kinase (MAPK or MAP kinase) is enriched by the amino acids serine and threonine. It is also referred to as a serine/threonine-specific protein kinase. Various stimuli like mitogen, heat shock, osmotic stress, and pro-inflammatory cytokines activate the MAPK pathway, which further regulates cell responses like cell proliferation, gene expression, mitosis, differentiation, cell survival, and apoptotic (Fig. 18.1) (Pearson et al. 2001). The MAPK cell signaling pathway is present from unicellular to multi-cellular eukaryotes. It is also in the groups of CMGC (CDK/MAPK/GSK3/CLK) kinases. The nearest link to MAPKs is Cyclin Dependent kinase (CDKs) (Manning 2002). The first MAPK is known as ERK1 (MAPK3) in mammals. Interestingly, most of the MAPKs show the following common characteristics (Coulombe and Meloche 2007):

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anne SL, Govek EE, Ayrault O, Kim JH, Zhu X, Murphy DA, Van Aelst L, Roussel MF, Hatten ME (2013) WNT3 inhibits cerebellar granule neuron progenitor proliferation and medulloblastoma formation via MAPK activation. PLoS One 8(11):e81769. https://doi.org/10.1371/journal.pone.0081769. PMID: 24303070; PMCID: PMC3841149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antonucci L, Di Magno L, D’Amico D, Manni S, Serrao SM, Di Pastena F, Bordone R, Yurtsever ZN, Caimano M, Petroni M, Giorgi A, Schininà ME, Yates Iii JR, Di Marcotullio L, De Smaele E, Checquolo S, Capalbo C, Agostinelli E, Maroder M, Coni S, Canettieri G (2019) Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation. Int J Oncol 54(2):505–514. https://doi.org/10.3892/ijo.2018.4638. Epub 2018 Nov 19. PMID: 30483764; PMCID: PMC6317670

    Article  CAS  PubMed  Google Scholar 

  • Azatyan A, Gallo-Oller G, Diao Y, Selivanova G, Johnsen JI, Zaphiropoulos PG (2019) RITA downregulates Hedgehog-GLI in medulloblastoma and rhabdomyosarcoma via JNK-dependent but p53-independent mechanism. Cancer Lett 442:341–350. https://doi.org/10.1016/j.canlet.2018.11.005. Epub 2018 Nov 14. PMID: 30447254

    Article  CAS  PubMed  Google Scholar 

  • Badodi S, Dubuc A, Zhang X, Rosser G, Da Cunha JM, Kameda-Smith MM, Morrissy AS, Guilhamon P, Suetterlin P, Li XN, Guglielmi L, Merve A, Farooq H, Lupien M, Singh SK, Basson MA, Taylor MD, Marino S (2017) Convergence of BMI1 and CHD7 on ERK signaling in medulloblastoma. Cell Rep 21(10):2772–2784. https://doi.org/10.1016/j.celrep.2017.11.021. PMID: 29212025; PMCID: PMC5732319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chou TT, Trojanowski JQ, Lee VM (2001) p38 mitogen-activated protein kinase-independent induction of gadd45 expression in nerve growth factor-induced apoptosis in medulloblastomas. J Biol Chem 276(44):41120–41127. https://doi.org/10.1074/jbc.M102832200. Epub 2001 Sep 5. PMID: 11544251

    Article  CAS  PubMed  Google Scholar 

  • Coulombe P, Meloche S (2007) Atypical mitogen-activated protein kinases: structure, regulation and functions. Biochim Biophys Acta 1773(8):1376–1387

    Article  CAS  PubMed  Google Scholar 

  • Gao R, Zhang R, Zhang C, Zhao L, Zhang Y (2018) Long noncoding RNA CCAT1 promotes cell proliferation and metastasis in human medulloblastoma via MAPK pathway. Tumori 104(1):43–50. https://doi.org/10.5301/tj.5000662. PMID: 28777430

    Article  CAS  PubMed  Google Scholar 

  • Guldal CG, Ahmad A, Korshunov A, Squatrito M, Awan A, Mainwaring LA, Bhatia B, Parathath SR, Nahle Z, Pfister S, Kenney AM (2012) An essential role for p38 MAPK in cerebellar granule neuron precursor proliferation. Acta Neuropathol 123(4):573–586. https://doi.org/10.1007/s00401-012-0946-z. PMID: 22302101; PMCID: PMC3775951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heavey S, O’Byrne KJ, Gately K (2014) Strategies for co-targeting the PI3K/AKT/mTOR pathway in NSCLC. Cancer Treat Rev 40(3):445–456. https://doi.org/10.1016/j.ctrv.2013.08.006. Epub 2013. PMID: 24055012

    Article  CAS  PubMed  Google Scholar 

  • Heavey S, Cuffe S, Finn S, Young V, Ryan R, Nicholson S, Leonard N, McVeigh N, Barr M, O’Byrne K (2016) Kathy Gately In pursuit of synergy: an investigation of the PI3K/mTOR/MEK co-targeted inhibition strategy in NSCLC. Oncotarget 7(48):79526–79543

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiabo Y, Sun X, Goie JYG, Zhang Y (2020) Regulation of host immune responses against influenza A virus infection by mitogen-activated protein kinases (MAPKs). Microorganisms 8(7):1067

    Article  Google Scholar 

  • Liang L, Coudière-Morrison L, Tatari N, Stromecki M, Fresnoza A, Porter CJ, Del Bigio MR, Hawkins C, Chan JA, Ryken TC, Taylor MD, Ramaswamy V, Werbowetski-Ogilvie TE (2018) CD271+ cells are diagnostic and prognostic and exhibit elevated MAPK activity in SHH medulloblastoma. Cancer Res 78(16):4745–4759. https://doi.org/10.1158/0008-5472.CAN-18-0027. Epub 2018 Jun 21. PMID: 29930101

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Liu L, Zheng M, Li X, Wu A, Wu Q, Liao C, Zou J, Song H (2018) MEKK2 and MEKK3 suppress Hedgehog pathway-dependent medulloblastoma by inhibiting GLI1 function. Oncogene 37(28):3864–3878. https://doi.org/10.1038/s41388-018-0249-5. Epub 2018 Apr 17. PMID: 29662197; PMCID: PMC6041257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacDonald TJ, Brown KM, LaFleur B, Peterson K, Lawlor C, Chen Y, Packer RJ, Cogen P, Stephan DA (2001) Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat Genet 29(2):143–152. https://doi.org/10.1038/ng731. Erratum in: Nat Genet. 2003;35(3):287. PMID: 11544480

    Article  CAS  PubMed  Google Scholar 

  • Markowitz D, Powell C, Tran NL, Berens ME, Ryken TC, Vanan M, Rosen L, He M, Sun S, Symons M, Al-Abed Y, Ruggieri R (2016) Pharmacological inhibition of the protein kinase MRK/ZAK radiosensitizes medulloblastoma. Mol Cancer Ther 15(8):1799–1808. https://doi.org/10.1158/1535-7163.MCT-15-0849. Epub 2016 May 20. PMID: 27207779

    Article  CAS  PubMed  Google Scholar 

  • Patti R, Reddy CD, Geoerger B, Grotzer MA, Raghunath M, Sutton LN, Phillips PC (2000) Autocrine secreted insulin-like growth factor-I stimulates MAP kinase-dependent mitogenic effects in human primitive neuroectodermal tumor/medulloblastoma. Int J Oncol 16(3):577–584. https://doi.org/10.3892/ijo.16.3.577. PMID: 10675492

    Article  CAS  PubMed  Google Scholar 

  • Pearson G, Robinson F, Gibson TB, Xu BE, Karandikar M, Berman K, Cobb MH (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22(2):153–183

    CAS  PubMed  Google Scholar 

  • Rao JS, Bhoopathi P, Chetty C, Gujrati M, Lakka SS (2007) MMP-9 short interfering RNA induced senescence resulting in inhibition of medulloblastoma growth via p16 (INK4a) and mitogen-activated protein kinase pathway. Cancer Res 67(10):4956–4964. https://doi.org/10.1158/0008-5472.CAN-07-0380. PMID: 17510426; PMCID: PMC1905835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi J-H, Sun S-C (2018) Tumor necrosis factor receptor-associated factor regulation of nuclear factor κB and mitogen-activated protein kinase pathways. Front Immunol 9:1849

    Article  PubMed  PubMed Central  Google Scholar 

  • Sturla LM, Cowan CW, Guenther L, Castellino RC, Kim JY, Pomeroy SL (2005) A novel role for extracellular signal-regulated kinase 5 and myocyte enhancer factor 2 in medulloblastoma cell death. Cancer Res 65(13):5683–5689. https://doi.org/10.1158/0008-5472.CAN-04-2283. PMID: 15994942

    Article  CAS  PubMed  Google Scholar 

  • Zhu LY, Wu XY, Liu XD, Zheng DF, Li HS, Yang B, Zhang J, Chang Q (2020) Aggressive medulloblastoma-derived exosomal miRNAs promote in vitro invasion and migration of tumor cells via Ras/MAPK pathway. J Neuropathol Exp Neurol 79(7):734–745. https://doi.org/10.1093/jnen/nlaa041. PMID: 32417918

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

    Mehdi Hayat Shahi

Authors
  1. Mehdi Hayat Shahi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Shahi, M.H. (2023). Mitogen-activated protein (MAP) kinase Roles in Paediatric Brain Tumor “Medulloblastoma”. In: Role of Signaling Pathways in Brain Tumorigenesis. Springer, Singapore. https://doi.org/10.1007/978-981-15-8473-2_18

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-8473-2_18

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-8472-5

  • Online ISBN: 978-981-15-8473-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation