KEGG   PATHWAY: dnm05226
Entry
dnm05226                    Pathway                                
Name
Gastric cancer - Dasypus novemcinctus (nine-banded armadillo)
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
dnm05226  Gastric cancer
dnm05226

Organism
Dasypus novemcinctus (nine-banded armadillo) [GN:dnm]
Gene
101422111  CDX2; homeobox protein CDX-2 isoform X2 [KO:K22234]
101446789  CDH17; cadherin-17 [KO:K06811]
101411292  REG4; regenerating islet-derived protein 4 isoform X1 [KO:K22244]
101432422  ABCB1; multidrug resistance protein 1 [KO:K05658] [EC:7.6.2.2]
101438572  SHH; sonic hedgehog protein [KO:K11988]
101416069  TP53; cellular tumor antigen p53 [KO:K04451]
101423941  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101447415  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101439228  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101418819  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101432154  BAX; apoptosis regulator BAX [KO:K02159]
101426878  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
101412187  DDB2; LOW QUALITY PROTEIN: DNA damage-binding protein 2 [KO:K10140]
101423502  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
101420553  retinoic acid receptor beta [KO:K08528]
101411907  RXRA; retinoic acid receptor RXR-alpha isoform X2 [KO:K08524]
101414688  RXRB; LOW QUALITY PROTEIN: retinoic acid receptor RXR-beta [KO:K08525]
101428198  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
101431125  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101432213  WNT2; protein Wnt-2 precursor [KO:K00182]
101436827  WNT2B; protein Wnt-2b [KO:K00182]
101447314  WNT3A; protein Wnt-3a [KO:K00312]
101416017  WNT3; proto-oncogene Wnt-3 [KO:K00312]
101425823  WNT4; protein Wnt-4 [KO:K00408]
101441152  WNT5B; protein Wnt-5b [KO:K00444]
101413304  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
101415471  WNT6; protein Wnt-6 [KO:K00445]
101428728  LOW QUALITY PROTEIN: protein Wnt-7a-like [KO:K00572]
101427420  WNT8B; protein Wnt-8b [KO:K00714]
101419396  WNT8A; protein Wnt-8a [KO:K00714]
101412391  WNT9A; LOW QUALITY PROTEIN: protein Wnt-9a [KO:K01064]
101444123  WNT9B; protein Wnt-9b [KO:K01064]
101430685  WNT10B; protein Wnt-10b isoform X2 [KO:K01357]
101435527  WNT10A; protein Wnt-10a [KO:K01357]
101443001  WNT11; protein Wnt-11 isoform X3 [KO:K01384]
101415111  WNT16; protein Wnt-16 [KO:K01558]
101426543  FZD1; frizzled-1 [KO:K02432]
101422116  FZD7; frizzled-7 [KO:K02432]
101443748  FZD2; LOW QUALITY PROTEIN: frizzled-2 [KO:K02235]
101417966  FZD3; frizzled-3 [KO:K02329]
101431024  FZD4; LOW QUALITY PROTEIN: frizzled-4 [KO:K02354]
101436426  FZD5; frizzled-5 [KO:K02375]
101434005  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
101426088  FZD6; frizzled-6 [KO:K02376]
101429184  FZD10; frizzled-10 [KO:K02842]
101437790  FZD9; frizzled-9 [KO:K02842]
101416179  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
101423227  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
101439692  DVL2; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
101435196  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
101411225  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
101447222  FRAT1; proto-oncogene FRAT1 [KO:K03069]
101434851  GSK-3-binding protein FRAT2 [KO:K03096]
101417330  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101411463  AXIN1; axin-1 [KO:K02157]
101412476  AXIN2; axin-2 isoform X1 [KO:K04385]
101412070  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
101415427  APC; adenomatous polyposis coli protein [KO:K02085]
101418767  CTNNB1; catenin beta-1 [KO:K02105]
101441952  LOW QUALITY PROTEIN: casein kinase I-like [KO:K08957] [EC:2.7.11.1]
101439209  CSNK1A1; casein kinase I [KO:K08957] [EC:2.7.11.1]
101411457  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
101417902  TCF7L1; transcription factor 7-like 1 [KO:K04490]
101433286  TCF7L2; LOW QUALITY PROTEIN: transcription factor 7-like 2 [KO:K04491]
101428006  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
101411312  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
101420648  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101410920  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
101418748  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
105746538  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
101425577  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
101438260  SHC1; SHC-transforming protein 1 [KO:K06279]
101447321  SHC2; SHC-transforming protein 2 [KO:K17447]
101417480  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
101422617  SHC4; SHC-transforming protein 4 [KO:K17449]
101422156  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101433544  SOS2; son of sevenless homolog 2 [KO:K03099]
101419480  HRAS; GTPase HRas isoform X1 [KO:K02833]
101412233  KRAS; GTPase KRas isoform X4 [KO:K07827]
101430817  NRAS; GTPase NRas [KO:K07828]
101414240  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
101419167  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101411989  BRAF; LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
101421211  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101435268  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101420546  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101430570  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101435742  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101444276  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101443761  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101426945  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101423744  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101435351  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101433347  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101419022  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101428799  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101445813  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101434069  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101439255  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101434210  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
101445333  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
101424272  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
101424995  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101413678  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
101440851  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
101411174  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
101441708  LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]
101414715  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
101421795  E2F3; transcription factor E2F3 [KO:K06620]
101437737  TGFB1; transforming growth factor beta-1 [KO:K13375]
101444912  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
101434549  TGFB3; transforming growth factor beta-3 [KO:K13377]
101411588  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
101430016  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
101429090  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
101447050  SMAD3; mothers against decapentaplegic homolog 3 isoform X2 [KO:K23605]
101427870  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101422825  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101418309  CDH1; cadherin-1 [KO:K05689]
101443374  CTNNA1; catenin alpha-1 [KO:K05691]
101423247  CTNNA3; catenin alpha-3 [KO:K05691]
101415519  JUP; junction plakoglobin [KO:K10056]
101445147  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
101437323  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
101425751  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
101423570  FGF2; fibroblast growth factor 2 [KO:K18497]
101433683  FGF5; fibroblast growth factor 5 [KO:K04358]
101436951  FGF7; fibroblast growth factor 7 [KO:K04358]
101444714  FGF6; fibroblast growth factor 6 [KO:K04358]
101443033  FGF10; fibroblast growth factor 10 [KO:K04358]
101421519  FGF4; fibroblast growth factor 4 [KO:K04358]
101421964  FGF3; fibroblast growth factor 3 [KO:K04358]
101442177  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
101422310  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
101447924  FGF20; fibroblast growth factor 20 [KO:K04358]
101415616  FGF9; fibroblast growth factor 9 [KO:K04358]
101428775  FGF16; fibroblast growth factor 16 [KO:K04358]
101429151  FGF18; fibroblast growth factor 18 [KO:K04358]
101421083  FGF19; fibroblast growth factor 19 [KO:K22603]
101422047  FGF21; fibroblast growth factor 21 [KO:K22429]
101415110  FGF23; fibroblast growth factor 23 [KO:K22428]
101412269  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
101447803  GAB1; GRB2-associated-binding protein 1 isoform X3 [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
dnm04010  MAPK signaling pathway
dnm04110  Cell cycle
dnm04115  p53 signaling pathway
dnm04151  PI3K-Akt signaling pathway
dnm04310  Wnt signaling pathway
dnm04350  TGF-beta signaling pathway
dnm04520  Adherens junction
KO pathway
ko05226   
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