KEGG   PATHWAY: uar05226
Entry
uar05226                    Pathway                                
Name
Gastric cancer - Ursus americanus (American black bear)
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
uar05226  Gastric cancer
uar05226

Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123791772  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
123775508  MUC2; mucin-2 [KO:K10955]
123797678  CDH17; cadherin-17 [KO:K06811]
123794925  REG4; regenerating islet-derived protein 4 [KO:K22244]
123789330  ABCB1; ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
123788743  SHH; sonic hedgehog protein [KO:K11988]
123792132  TP53; cellular tumor antigen p53 [KO:K04451]
123779575  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
123793985  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
123795328  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
123776460  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
123776228  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
123790912  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
123785020  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
123800189  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
123788327  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
123775752  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
123790933  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
123800144  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
123794641  WNT1; proto-oncogene Wnt-1 [KO:K03209]
123795067  WNT2B; protein Wnt-2b [KO:K00182]
123789031  WNT2; protein Wnt-2 [KO:K00182]
123803212  WNT3; proto-oncogene Wnt-3 [KO:K00312]
123797350  WNT3A; LOW QUALITY PROTEIN: protein Wnt-3a [KO:K00312]
123782322  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
123798771  WNT5A; protein Wnt-5a [KO:K00444]
123778248  WNT5B; protein Wnt-5b [KO:K00444]
123779462  WNT6; protein Wnt-6 [KO:K00445]
123802020  WNT7A; protein Wnt-7a [KO:K00572]
123780840  WNT7B; protein Wnt-7b [KO:K00572]
123795867  WNT8B; protein Wnt-8b [KO:K00714]
123790582  WNT8A; protein Wnt-8a [KO:K00714]
123803160  WNT9B; protein Wnt-9b [KO:K01064]
123797351  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
123794643  WNT10B; protein Wnt-10b [KO:K01357]
123779460  WNT10A; protein Wnt-10a [KO:K01357]
123804241  WNT11; protein Wnt-11 [KO:K01384]
123789562  WNT16; protein Wnt-16 [KO:K01558]
123789304  FZD1; frizzled-1 [KO:K02432]
123798210  FZD7; frizzled-7 [KO:K02432]
123802992  FZD2; frizzled-2 [KO:K02235]
123777397  FZD3; frizzled-3 [KO:K02329]
123803840  FZD4; frizzled-4 [KO:K02354]
123784863  FZD8; frizzled-8 [KO:K02375]
123798254  FZD5; frizzled-5 [KO:K02375]
123797814  FZD6; frizzled-6 [KO:K02376]
123780512  FZD10; frizzled-10 [KO:K02842]
123784748  FZD9; frizzled-9 [KO:K02842]
123781781  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
123778354  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
123792171  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
123796097  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
123778942  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
123783969  FRAT1; proto-oncogene FRAT1 [KO:K03069]
123783968  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
123784023  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
123783241  AXIN1; axin-1 isoform X1 [KO:K02157]
123803074  AXIN2; axin-2 isoform X1 [KO:K04385]
123794019  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
123779308  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
123792803  CTNNB1; catenin beta-1 [KO:K02105]
123803631  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
123790349  TCF7; transcription factor 7 isoform X1 [KO:K02620]
123799645  TCF7L1; LOW QUALITY PROTEIN: transcription factor 7-like 1 [KO:K04490]
123795969  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
123793375  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
123801908  MYC; myc proto-oncogene protein [KO:K04377]
123778441  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
123799097  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
123793362  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
123786270  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
123779529  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
123783413  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
123794070  LOW QUALITY PROTEIN: SHC-transforming protein 2-like [KO:K17447]
123776524  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
123801854  SHC4; SHC-transforming protein 4 [KO:K17449]
123802938  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123799809  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123793291  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
123775506  HRAS; GTPase HRas isoform X1 [KO:K02833]
123801699  KRAS; GTPase KRas isoform X1 [KO:K07827]
123795037  NRAS; GTPase NRas [KO:K07828]
123786515  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
123788872  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
123802053  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123800861  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
123796818  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123795639  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123784602  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123786407  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123788422  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123779078  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123800228  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123793748  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
123779926  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123793473  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123784096  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123791373  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123779112  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
123778404  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
123777184  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
123787450  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
123792845  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
123781751  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
123787272  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
123797872  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
123791375  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
123791847  RB1; retinoblastoma-associated protein [KO:K06618]
123798360  E2F1; transcription factor E2F1 [KO:K17454]
123782351  E2F2; transcription factor E2F2 [KO:K09389]
123791040  E2F3; LOW QUALITY PROTEIN: transcription factor E2F3 [KO:K06620]
123781846  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
123800112  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
123798962  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
123781069  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
123777686  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
123787367  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
123800821  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
123787394  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
123781261  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
123803436  CDH1; cadherin-1 [KO:K05689]
123776641  LOW QUALITY PROTEIN: cadherin-1-like [KO:K05689]
123783007  CTNNA3; catenin alpha-3 [KO:K05691]
123790298  CTNNA1; catenin alpha-1 [KO:K05691]
123781852  junction plakoglobin [KO:K10056]
123789349  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
123789034  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
123790206  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
123793143  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
123785536  FGF10; fibroblast growth factor 10 [KO:K04358]
123794063  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
123801808  FGF7; fibroblast growth factor 7 isoform X1 [KO:K04358]
123780440  FGF20; fibroblast growth factor 20 [KO:K04358]
123794868  FGF16; fibroblast growth factor 16 [KO:K04358]
123781579  FGF6; fibroblast growth factor 6 isoform X1 [KO:K04358]
123788636  FGF18; fibroblast growth factor 18 [KO:K04358]
123795836  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
123789204  FGF5; fibroblast growth factor 5 [KO:K04358]
123791977  FGF9; fibroblast growth factor 9 [KO:K04358]
123778359  FGF4; LOW QUALITY PROTEIN: fibroblast growth factor 4 [KO:K04358]
123778371  FGF3; fibroblast growth factor 3 [KO:K04358]
123777458  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
123778372  FGF19; fibroblast growth factor 19 [KO:K22603]
123776278  FGF21; fibroblast growth factor 21 [KO:K22429]
123781630  FGF23; fibroblast growth factor 23 [KO:K22428]
123796025  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
123793251  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
PMID:26073375
  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
PMID:26267324
  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
PMID:16154715
  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
PMID:18381231
  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
PMID:16997151
  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
PMID:16718776
  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
PMID:15224192
  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
PMID:12894247
  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
PMID:28427431
  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
PMID:24744585
  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
PMID:11683489
  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
PMID:26857262
  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
PMID:24061039
  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
PMID:26071484
  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
PMID:22042966
  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
PMID:19318488
  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
PMID:22586678
  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
PMID:23696246
  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
PMID:19387476
  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
PMID:20836672
  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
uar04010  MAPK signaling pathway
uar04110  Cell cycle
uar04115  p53 signaling pathway
uar04151  PI3K-Akt signaling pathway
uar04310  Wnt signaling pathway
uar04350  TGF-beta signaling pathway
uar04520  Adherens junction
KO pathway
ko05226   
LinkDB

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