KEGG   PATHWAY: oaa05226
Entry
oaa05226                    Pathway                                
Name
Gastric cancer - Ornithorhynchus anatinus (platypus)
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
oaa05226  Gastric cancer
oaa05226

Organism
Ornithorhynchus anatinus (platypus) [GN:oaa]
Gene
114805927  CDX2; homeobox protein CDX-2 [KO:K22234]
100086510  MUC2; LOW QUALITY PROTEIN: mucin-2 [KO:K10955]
100074203  CDH17; cadherin-17 [KO:K06811]
100077826  ABCB1; ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
100081692  SHH; sonic hedgehog protein [KO:K11988]
100092821  TP53; cellular tumor antigen p53 [KO:K04451]
114813305  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100081893  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
114814649  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
114813317  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100088212  DDB2; DNA damage-binding protein 2 [KO:K10140]
100077423  POLK; DNA polymerase kappa isoform X2 [KO:K03511] [EC:2.7.7.7]
100075704  retinoic acid receptor beta isoform X1 [KO:K08528]
114813900  retinoic acid receptor beta-like [KO:K08528]
100074625  retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
114811257  retinoic acid receptor RXR-alpha-like [KO:K08524]
114817203  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
114814562  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100077640  WNT2; protein Wnt-2 precursor [KO:K00182]
100087253  WNT2B; protein Wnt-2b [KO:K00182]
100090103  WNT3A; LOW QUALITY PROTEIN: protein Wnt-3a [KO:K00312]
100075238  WNT4; protein Wnt-4 [KO:K00408]
100085809  WNT5B; protein Wnt-5b [KO:K00444]
100088897  WNT5A; protein Wnt-5a [KO:K00444]
100089786  WNT6; protein Wnt-6 [KO:K00445]
100075994  WNT7A; protein Wnt-7a [KO:K00572]
100093588  WNT7B; protein Wnt-7b [KO:K00572]
100088910  protein Wnt-7a-like [KO:K00572]
100079874  WNT8B; protein Wnt-8b [KO:K00714]
100085370  WNT8A; protein Wnt-8a [KO:K00714]
100074117  WNT9A; protein Wnt-9a [KO:K01064]
100090678  WNT10A; protein Wnt-10a [KO:K01357]
107547159  WNT10B; protein Wnt-10b [KO:K01357]
100091700  WNT11; protein Wnt-11 [KO:K01384]
100077974  WNT16; protein Wnt-16 [KO:K01558]
100081860  FZD7; frizzled-7 [KO:K02432]
114813907  FZD1; frizzled-1 [KO:K02432]
100090775  FZD2; frizzled-2 [KO:K02235]
100086058  FZD3; frizzled-3 [KO:K02329]
100080994  FZD4; frizzled-4 [KO:K02354]
100089547  FZD5; LOW QUALITY PROTEIN: frizzled-5 [KO:K02375]
114816216  FZD8; frizzled-8 [KO:K02375]
100080710  FZD6; frizzled-6 [KO:K02376]
100091844  FZD10; frizzled-10 [KO:K02842]
100080214  FZD9; frizzled-9 [KO:K02842]
100077194  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
100091980  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100089867  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
100681615  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
114810222  GSK-3-binding protein FRAT2-like [KO:K03096]
100092089  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100093450  AXIN1; axin-1 [KO:K02157]
100077932  AXIN2; axin-2 [KO:K04385]
100082114  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
100682203  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
100080628  CTNNB1; catenin beta-1 [KO:K02105]
100076676  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
100082332  TCF7; transcription factor 7 isoform X1 [KO:K02620]
114817948  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100080633  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
100079818  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
100079391  MYC; myc proto-oncogene protein [KO:K04377]
100075081  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102060413  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
100074960  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
100075894  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
100091139  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
114808180  SHC1; SHC-transforming protein 1 [KO:K06279]
100081397  SHC2; SHC-transforming protein 2 [KO:K17447]
100075806  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100084645  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100078989  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
114809992  HRAS; GTPase HRas [KO:K02833]
100085430  KRAS; GTPase KRas isoform X1 [KO:K07827]
100074671  NRAS; GTPase NRas [KO:K07828]
100084423  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
100086380  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
100089456  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100080362  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100087942  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100085480  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100086487  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100086270  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100073788  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100074273  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100080187  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
100082075  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
103167126  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100083320  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100081473  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100090267  AKT2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100079751  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
100087780  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100078852  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
114807635  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100073765  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
100090228  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
114814505  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100075784  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
100087197  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
100083537  RB1; retinoblastoma-associated protein [KO:K06618]
100087014  E2F1; transcription factor E2F1 [KO:K17454]
100085053  E2F2; transcription factor E2F2 [KO:K09389]
100090475  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
114812005  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
100080176  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
100074840  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
100092358  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
100076965  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100085963  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100077136  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
114807863  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
100079609  CDH1; cadherin-1 [KO:K05689]
100077885  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
100091564  CTNNA1; catenin alpha-1 isoform X1 [KO:K05691]
100080184  CTNNA3; LOW QUALITY PROTEIN: catenin alpha-3 [KO:K05691]
100086720  junction plakoglobin isoform X1 [KO:K10056]
100074892  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
100079345  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
100078822  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
114815531  FGF2; fibroblast growth factor 2 [KO:K18497]
100075228  FGF4; fibroblast growth factor 4 [KO:K04358]
100075300  FGF3; LOW QUALITY PROTEIN: fibroblast growth factor 3 [KO:K04358]
100089319  FGF9; fibroblast growth factor 9 [KO:K04358]
100073730  FGF5; fibroblast growth factor 5 [KO:K04358]
100093377  FGF18; fibroblast growth factor 18 [KO:K04358]
100089414  FGF22; fibroblast growth factor 22 [KO:K04358]
100088500  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
100089135  FGF20; fibroblast growth factor 20 [KO:K04358]
100080372  FGF8; fibroblast growth factor 8 [KO:K04358]
100075757  FGF10; fibroblast growth factor 10 [KO:K04358]
103165700  FGF6; fibroblast growth factor 6 [KO:K04358]
100084373  FGF16; fibroblast growth factor 16 [KO:K04358]
114813732  FGF7; fibroblast growth factor 7 [KO:K04358]
100075189  FGF19; fibroblast growth factor 19 [KO:K22603]
114807786  FGF23; fibroblast growth factor 23 [KO:K22428]
100084641  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
100082582  GAB1; 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
oaa04010  MAPK signaling pathway
oaa04110  Cell cycle
oaa04115  p53 signaling pathway
oaa04151  PI3K-Akt signaling pathway
oaa04310  Wnt signaling pathway
oaa04350  TGF-beta signaling pathway
oaa04520  Adherens junction
KO pathway
ko05226   
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