KEGG   PATHWAY: aju05226
Entry
aju05226                    Pathway                                
Name
Gastric cancer - Acinonyx jubatus (cheetah)
Description
Gastric cancer (GC) is one of the world's most common cancers. According to Lauren's histological classification gastric cancer is divided into two distinct histological groups - the intestinal and diffuse types. Several genetic changes have been identified in intestinal-type GC. The intestinal metaplasia is characterized by mutations in p53 gene, reduced expression of retinoic acid receptor beta (RAR-beta) and hTERT expression. Gastric adenomas furthermore display mutations in the APC gene, reduced p27 expression and cyclin E amplification. In addition, amplification and overexpression of c-ErbB2, reduced TGF-beta receptor type I (TGFBRI) expression and complete loss of p27 expression are commonly observed in more advanced GC. The main molecular changes observed in diffuse-type GCs include loss of E-cadherin function by mutations in CDH1 and amplification of MET and FGFR2F.
Class
Human Diseases; Cancer: specific types
Pathway map
aju05226  Gastric cancer
aju05226

Organism
Acinonyx jubatus (cheetah) [GN:aju]
Gene
113601155  homeobox protein CDX-2 isoform X1 [KO:K22234]
106974891  cadherin-17 isoform X4 [KO:K06811]
106978506  regenerating islet-derived protein 4 [KO:K22244]
106987581  ATP-dependent translocase ABCB1 isoform X2 [KO:K05658] [EC:7.6.2.2]
113596760  sonic hedgehog protein isoform X1 [KO:K11988]
106972437  cellular tumor antigen p53 [KO:K04451]
106972797  cyclin-dependent kinase inhibitor 1 [KO:K06625]
106989693  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
106985200  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
113594268  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
106988699  apoptosis regulator BAX isoform X1 [KO:K02159]
106976101  bcl-2 homologous antagonist/killer [KO:K14021]
106978021  DNA damage-binding protein 2 isoform X2 [KO:K10140]
106974834  DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
106988245  retinoic acid receptor beta isoform X1 [KO:K08528]
106988254  retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
106976118  retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
106965571  retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
106969330  proto-oncogene Wnt-1 [KO:K03209]
106969623  protein Wnt-2b [KO:K00182]
106970665  protein Wnt-2 [KO:K00182]
106985206  protein Wnt-3a [KO:K00312]
106988834  proto-oncogene Wnt-3 isoform X3 [KO:K00312]
113599491  protein Wnt-4 isoform X1 [KO:K00408]
106967018  protein Wnt-5a isoform X1 [KO:K00444]
106965408  protein Wnt-5b isoform X3 [KO:K00444]
106970073  protein Wnt-6 [KO:K00445]
106978815  protein Wnt-7a isoform X1 [KO:K00572]
113602684  protein Wnt-7b isoform X2 [KO:K00572]
106966936  protein Wnt-8b [KO:K00714]
106968544  protein Wnt-8a [KO:K00714]
106985205  protein Wnt-9a isoform X1 [KO:K01064]
106988831  protein Wnt-9b [KO:K01064]
106970053  protein Wnt-10a [KO:K01357]
106969331  protein Wnt-10b [KO:K01357]
106976446  protein Wnt-11 [KO:K01384]
106970656  protein Wnt-16 [KO:K01558]
106978285  frizzled-7 [KO:K02432]
106987276  frizzled-1 [KO:K02432]
106974284  frizzled-2 [KO:K02235]
106983024  frizzled-3 isoform X2 [KO:K02329]
106967740  frizzled-4 [KO:K02354]
106967100  frizzled-5 [KO:K02375]
113603657  frizzled-8 [KO:K02375]
106980059  frizzled-6 [KO:K02376]
106986936  frizzled-10 [KO:K02842]
106980711  frizzled-9 [KO:K02842]
106965642  low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
106971089  low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
106988759  segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
106983787  segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
106972415  segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
113600380  proto-oncogene FRAT1 [KO:K03069]
128312599  GSK-3-binding protein FRAT2 [KO:K03096]
106968274  glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
106977359  axin-1 isoform X1 [KO:K02157]
106975307  axin-2 isoform X1 [KO:K04385]
106973163  adenomatous polyposis coli protein isoform X3 [KO:K02085]
106983719  adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
106966666  catenin beta-1 [KO:K02105]
106985401  casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
106984911  LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
106978197  transcription factor 7-like 1 isoform X1 [KO:K04490]
106974119  transcription factor 7-like 2 isoform X1 [KO:K04491]
106983664  lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
106976895  myc proto-oncogene protein [KO:K04377]
106971167  G1/S-specific cyclin-D1 [KO:K04503]
106985112  telomerase reverse transcriptase isoform X9 [KO:K11126] [EC:2.7.7.49]
106983657  LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
106976977  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
106980462  receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
106988382  SHC-transforming protein 1 isoform X1 [KO:K06279]
106978092  SHC-transforming protein 2 isoform X1 [KO:K17447]
106987970  SHC-transforming protein 3 [KO:K17448]
106967221  SHC-transforming protein 4 isoform X1 [KO:K17449]
106987795  growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
106978987  son of sevenless homolog 1 isoform X1 [KO:K03099]
106989073  son of sevenless homolog 2 isoform X1 [KO:K03099]
106987957  GTPase HRas isoform X1 [KO:K02833]
106968778  GTPase KRas isoform X1 [KO:K07827]
106969596  GTPase NRas [KO:K07828]
106972677  serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
106970441  serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
106977129  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
106980282  dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
106975474  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106969232  mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
106990008  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106984896  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106984265  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106973880  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106976917  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
106973297  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
106969150  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
106979622  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
106975558  RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
106985046  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106984907  serine/threonine-protein kinase mTOR isoform X2 [KO:K07203] [EC:2.7.11.1]
106972702  ribosomal protein S6 kinase beta-1 isoform X2 [KO:K04688] [EC:2.7.11.1]
106971103  ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
106985187  apoptosis regulator Bcl-2 [KO:K02161]
106982621  DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
106965649  cyclin-dependent kinase inhibitor 1B [KO:K06624]
106986916  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
106974883  G1/S-specific cyclin-E2 [KO:K06626]
106975766  G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
106971960  retinoblastoma-associated protein isoform X1 [KO:K06618]
106974609  transcription factor E2F1 isoform X2 [KO:K17454]
106977597  transcription factor E2F2 [KO:K09389]
106987605  transcription factor E2F3 isoform X3 [KO:K06620]
106987682  transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
106979500  transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
106974351  transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
106972043  TGF-beta receptor type-1 isoform X3 [KO:K04674] [EC:2.7.11.30]
106984570  TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
106972947  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
106980367  mothers against decapentaplegic homolog 3 isoform X3 [KO:K23605]
106974966  mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
106986385  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
106972406  cadherin-1 [KO:K05689]
106967933  catenin alpha-1 isoform X1 [KO:K05691]
106978213  catenin alpha-2 isoform X1 [KO:K05691]
106967186  catenin alpha-3 isoform X1 [KO:K05691]
106972560  junction plakoglobin isoform X2 [KO:K10056]
106975661  hepatocyte growth factor isoform X1 [KO:K05460]
106970667  hepatocyte growth factor receptor isoform X2 [KO:K05099] [EC:2.7.10.1]
106967134  fibroblast growth factor 1 isoform X1 [KO:K18496]
106977090  fibroblast growth factor 2 [KO:K18497]
106966945  fibroblast growth factor 8 [KO:K04358]
106967112  fibroblast growth factor 10 [KO:K04358]
106967225  fibroblast growth factor 7 isoform X1 [KO:K04358]
106965488  fibroblast growth factor 6 [KO:K04358]
106972632  fibroblast growth factor 20 [KO:K04358]
106976900  fibroblast growth factor 5 isoform X1 [KO:K04358]
106988440  fibroblast growth factor 16 [KO:K04358]
106979814  fibroblast growth factor 9 [KO:K04358]
106981101  fibroblast growth factor 17 isoform X1 [KO:K04358]
106973440  fibroblast growth factor 18 [KO:K04358]
113595410  fibroblast growth factor 3 [KO:K04358]
113596382  fibroblast growth factor 22 [KO:K04358]
113595513  fibroblast growth factor 4 [KO:K04358]
128311660  fibroblast growth factor 19 [KO:K22603]
106988712  fibroblast growth factor 21 [KO:K22429]
106965456  fibroblast growth factor 23 [KO:K22428]
106969379  fibroblast growth factor receptor 2 isoform X3 [KO:K05093] [EC:2.7.10.1]
106983704  GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
Compound
C00039  DNA
C00777  Retinoate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C15493  9-cis-Retinoic acid
Reference
  Authors
Tan P, Yeoh KG
  Title
Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma.
  Journal
Gastroenterology 149:1153-1162.e3 (2015)
DOI:10.1053/j.gastro.2015.05.059
Reference
  Authors
Riquelme I, Saavedra K, Espinoza JA, Weber H, Garcia P, Nervi B, Garrido M, Corvalan AH, Roa JC, Bizama C
  Title
Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy.
  Journal
Oncotarget 6:24750-79 (2015)
DOI:10.18632/oncotarget.4990
Reference
  Authors
Stock M, Otto F
  Title
Gene deregulation in gastric cancer.
  Journal
Gene 360:1-19 (2005)
DOI:10.1016/j.gene.2005.06.026
Reference
  Authors
Panani AD
  Title
Cytogenetic and molecular aspects of gastric cancer: clinical implications.
  Journal
Cancer Lett 266:99-115 (2008)
DOI:10.1016/j.canlet.2008.02.053
Reference
  Authors
Vauhkonen M, Vauhkonen H, Sipponen P
  Title
Pathology and molecular biology of gastric cancer.
  Journal
Best Pract Res Clin Gastroenterol 20:651-74 (2006)
DOI:10.1016/j.bpg.2006.03.016
Reference
  Authors
Smith MG, Hold GL, Tahara E, El-Omar EM.
  Title
Cellular and molecular aspects of gastric cancer.
  Journal
World J Gastroenterol 12:2979-90 (2006)
DOI:10.3748/wjg.v12.i19.2979
Reference
  Authors
Zheng L, Wang L, Ajani J, Xie K.
  Title
Molecular basis of gastric cancer development and progression.
  Journal
Gastric Cancer 7:61-77 (2004)
DOI:10.1007/s10120-004-0277-4
Reference
  Authors
Yuasa Y
  Title
Control of gut differentiation and intestinal-type gastric carcinogenesis.
  Journal
Nat Rev Cancer 3:592-600 (2003)
DOI:10.1038/nrc1141
Reference
  Authors
Wessler S, Krisch LM, Elmer DP, Aberger F
  Title
From inflammation to gastric cancer - the importance of Hedgehog/GLI signaling in Helicobacter pylori-induced chronic inflammatory and neoplastic diseases.
  Journal
Cell Commun Signal 15:15 (2017)
DOI:10.1186/s12964-017-0171-4
Reference
  Authors
Yan LH, Wei WY, Xie YB, Xiao Q
  Title
New insights into the functions and localization of the homeotic gene CDX2 in gastric cancer.
  Journal
World J Gastroenterol 20:3960-6 (2014)
DOI:10.3748/wjg.v20.i14.3960
Reference
  Authors
Hayashi K, Yokozaki H, Goodison S, Oue N, Suzuki T, Lotan R, Yasui W, Tahara E
  Title
Inactivation of retinoic acid receptor beta by promoter CpG hypermethylation in gastric cancer.
  Journal
Differentiation 68:13-21 (2001)
DOI:10.1046/j.1432-0436.2001.068001013.x
Reference
  Authors
Li X, Wu WK, Xing R, Wong SH, Liu Y, Fang X, Zhang Y, Wang M, Wang J, Li L, Zhou Y, Tang S, Peng S, Qiu K, Chen L, Chen K, Yang H, Zhang W, Chan MT, Lu Y, Sung JJ, Yu J
  Title
Distinct Subtypes of Gastric Cancer Defined by Molecular Characterization Include Novel Mutational Signatures with Prognostic Capability.
  Journal
Cancer Res 76:1724-32 (2016)
DOI:10.1158/0008-5472.CAN-15-2443
Reference
  Authors
Wadhwa R, Song S, Lee JS, Yao Y, Wei Q, Ajani JA
  Title
Gastric cancer-molecular and clinical dimensions.
  Journal
Nat Rev Clin Oncol 10:643-55 (2013)
DOI:10.1038/nrclinonc.2013.170
Reference
  Authors
Bertotti A, Sassi F
  Title
Molecular Pathways: Sensitivity and Resistance to Anti-EGFR Antibodies.
  Journal
Clin Cancer Res 21:3377-83 (2015)
DOI:10.1158/1078-0432.CCR-14-0848
Reference
  Authors
Appleman LJ
  Title
MET signaling pathway: a rational target for cancer therapy.
  Journal
J Clin Oncol 29:4837-8 (2011)
DOI:10.1200/JCO.2011.37.7929
Reference
  Authors
Eder JP, Vande Woude GF, Boerner SA, LoRusso PM
  Title
Novel therapeutic inhibitors of the c-Met signaling pathway in cancer.
  Journal
Clin Cancer Res 15:2207-14 (2009)
DOI:10.1158/1078-0432.CCR-08-1306
Reference
  Authors
Feng Y, Ma PC
  Title
Anti-MET targeted therapy has come of age: the first durable complete response with MetMAb in metastatic gastric cancer.
  Journal
Cancer Discov 1:550-4 (2011)
DOI:10.1158/2159-8290.CD-11-0289
Reference
  Authors
Katoh M, Nakagama H
  Title
FGF receptors: cancer biology and therapeutics.
  Journal
Med Res Rev 34:280-300 (2014)
DOI:10.1002/med.21288
Reference
  Authors
Katoh M
  Title
FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies.
  Journal
J Invest Dermatol 129:1861-7 (2009)
DOI:10.1038/jid.2009.97
Reference
  Authors
Katoh M
  Title
Genetic alterations of FGF receptors: an emerging field in clinical cancer diagnostics and therapeutics.
  Journal
Expert Rev Anticancer Ther 10:1375-9 (2010)
DOI:10.1586/era.10.128
Related
pathway
aju04010  MAPK signaling pathway
aju04110  Cell cycle
aju04115  p53 signaling pathway
aju04151  PI3K-Akt signaling pathway
aju04310  Wnt signaling pathway
aju04350  TGF-beta signaling pathway
aju04520  Adherens junction
KO pathway
ko05226   
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