KEGG   PATHWAY: rro05214
Entry
rro05214                    Pathway                                
Name
Glioma - Rhinopithecus roxellana (golden snub-nosed monkey)
Description
Gliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (astrocytomas), oligodendrocytes (oligodendrogliomas), mixtures of various glial cells (for example,oligoastrocytomas) and ependymal cells (ependymomas). The most malignant form of infiltrating astrocytoma - glioblastoma multiforme (GBM) - is one of the most aggressive human cancers. GBM may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). Primary glioblastomas develop in older patients and typically show genetic alterations (EGFR amplification, p16/INK4a deletion, and PTEN mutations) at frequencies of 24-34%. Secondary glioblastomas develop in younger patients and frequently show overexpression of PDGF and CDK4 as well as p53 mutations (65%) and loss of Rb playing major roles in such transformations. Loss of PTEN has been implicated in both pathways, although it is much more common in the pathogenesis of primary GBM.
Class
Human Diseases; Cancer: specific types
Pathway map
rro05214  Glioma
rro05214

Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104682421  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
104661322  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
104675886  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
104664975  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
104682558  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
104658857  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
104670408  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
104657459  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
104677192  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
104672220  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
104671624  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
104662055  calmodulin [KO:K02183]
104663170  CALM2; calmodulin-2 [KO:K02183]
104680741  calmodulin-alpha-like [KO:K02183]
104670544  CALM1; calmodulin-1 [KO:K02183]
104673406  CALM3; calmodulin-3 [KO:K02183]
104664834  CALML5; calmodulin-like protein 5 [KO:K02183]
104664835  CALML3; calmodulin-like protein 3 [KO:K02183]
104653554  CALML6; calmodulin-like protein 6 isoform X2 [KO:K02183]
104662590  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
104674211  calmodulin-alpha-like [KO:K02183]
104656871  calmodulin-like [KO:K02183]
104664168  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
104664882  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
104676623  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
104670410  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
104671146  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
104669984  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
104677657  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
104675428  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
104665907  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
104676027  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
104663483  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
104668515  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
104657941  SHC4; SHC-transforming protein 4 [KO:K17449]
104681311  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
104663024  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
104682751  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
104654600  HRAS; GTPase HRas isoform X1 [KO:K02833]
104670041  KRAS; GTPase KRas isoform X1 [KO:K07827]
104669078  NRAS; GTPase NRas [KO:K07828]
104664593  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
104659700  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
104673299  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
104662575  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104665487  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104676897  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104681150  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104663050  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104665061  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104670605  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104662124  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104675620  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104680672  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104673041  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104676121  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104654186  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
115893905  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104654362  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
104675158  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
104654275  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
104658667  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
104661662  TP53; cellular tumor antigen p53 [KO:K04451]
104682880  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
104677168  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104682344  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
104682750  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
104662760  RB1; retinoblastoma-associated protein [KO:K06618]
104660298  E2F1; transcription factor E2F1 [KO:K17454]
104656129  E2F2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
104654803  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
104671382  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
104657306  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
104656307  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104666540  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
104658958  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
104668405  DDB2; DNA damage-binding protein 2 [KO:K10140]
104653753  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:15639402
  Authors
Soni D, King JA, Kaye AH, Hovens CM.
  Title
Genetics of glioblastoma multiforme: mitogenic signaling and cell cycle pathways converge.
  Journal
J Clin Neurosci 12:1-5 (2005)
DOI:10.1016/j.jocn.2004.04.001
Reference
PMID:12154354
  Authors
Zhu Y, Parada LF.
  Title
The molecular and genetic basis of neurological tumours.
  Journal
Nat Rev Cancer 2:616-26 (2002)
DOI:10.1038/nrc866
Reference
PMID:11253051
  Authors
Holland EC.
  Title
Gliomagenesis: genetic alterations and mouse models.
  Journal
Nat Rev Genet 2:120-9 (2001)
DOI:10.1038/35052535
Reference
PMID:16700615
  Authors
Bansal K, Liang ML, Rutka JT.
  Title
Molecular biology of human gliomas.
  Journal
Technol Cancer Res Treat 5:185-94 (2006)
DOI:10.1177/153303460600500302
Reference
  Authors
Tabuchi K (ed).
  Title
[Gliomas: Research and therapy] (In Japanese)
  Journal
Springer-Verlag Tokyo (2006)
Reference
PMID:12762887
  Authors
Kapoor GS, O'Rourke DM.
  Title
Mitogenic signaling cascades in glial tumors.
  Journal
Neurosurgery 52:1425-34; discussion 1434-5 (2003)
DOI:10.1227/01.NEU.0000065135.28143.39
Reference
PMID:16095998
  Authors
Hulleman E, Helin K.
  Title
Molecular mechanisms in gliomagenesis.
  Journal
Adv Cancer Res 94:1-27 (2005)
DOI:10.1016/S0065-230X(05)94001-3
Reference
PMID:11057895
  Authors
Schlessinger J.
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 103:211-25 (2000)
DOI:10.1016/S0092-8674(00)00114-8
Reference
PMID:9643506
  Authors
Ng HK, Lam PY.
  Title
The molecular genetics of central nervous system tumors.
  Journal
Pathology 30:196-202 (1998)
DOI:10.1080/00313029800169236
Reference
PMID:12084351
  Authors
Knobbe CB, Merlo A, Reifenberger G.
  Title
Pten signaling in gliomas.
  Journal
Neuro-oncol 4:196-211 (2002)
DOI:10.1093/neuonc/4.3.196
Related
pathway
rro04010  MAPK signaling pathway
rro04012  ErbB signaling pathway
rro04020  Calcium signaling pathway
rro04060  Cytokine-cytokine receptor interaction
rro04110  Cell cycle
rro04115  p53 signaling pathway
rro04150  mTOR signaling pathway
KO pathway
ko05214   
LinkDB

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