KEGG   PATHWAY: eai05226
Entry
eai05226                    Pathway                                
Name
Gastric cancer - Equus asinus (ass)
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
eai05226  Gastric cancer
eai05226

Organism
Equus asinus (ass) [GN:eai]
Gene
106832905  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
106825295  LOW QUALITY PROTEIN: mucin-2-like [KO:K10955]
106824950  LOW QUALITY PROTEIN: mucin-2-like [KO:K10955]
106831448  CDH17; cadherin-17 [KO:K06811]
123277756  REG4; LOW QUALITY PROTEIN: regenerating islet-derived protein 4 [KO:K22244]
106844768  ABCB1; ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
106823318  SHH; LOW QUALITY PROTEIN: sonic hedgehog protein [KO:K11988]
106844218  TP53; cellular tumor antigen p53 [KO:K04451]
106824579  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
106834158  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
106825069  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
106825118  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
106838268  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
106834586  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
106844006  DDB2; DNA damage-binding protein 2 [KO:K10140]
106824006  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
106823884  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
106845341  RXRA; retinoic acid receptor RXR-alpha isoform X2 [KO:K08524]
106834605  RXRB; retinoic acid receptor RXR-beta isoform X3 [KO:K08525]
106831132  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
106836901  WNT1; proto-oncogene Wnt-1 [KO:K03209]
106829346  WNT2; protein Wnt-2 [KO:K00182]
106828591  WNT2B; protein Wnt-2b [KO:K00182]
106836509  WNT3; proto-oncogene Wnt-3 [KO:K00312]
106821809  WNT3A; protein Wnt-3a [KO:K00312]
106840003  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
106848670  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
106824632  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
106838461  WNT6; protein Wnt-6 isoform X3 [KO:K00445]
106829376  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
106845973  WNT7B; protein Wnt-7b isoform X2 [KO:K00572]
106839204  WNT8A; protein Wnt-8a isoform X3 [KO:K00714]
106846753  WNT8B; protein Wnt-8b [KO:K00714]
106836490  WNT9B; protein Wnt-9b [KO:K01064]
106821810  protein Wnt-9a [KO:K01064]
123289075  LOW QUALITY PROTEIN: protein Wnt-9a-like [KO:K01064]
106836816  WNT10B; protein Wnt-10b [KO:K01357]
106838468  WNT10A; protein Wnt-10a [KO:K01357]
106840396  WNT11; LOW QUALITY PROTEIN: protein Wnt-11 [KO:K01384]
106829817  WNT16; protein Wnt-16 [KO:K01558]
106843140  FZD7; frizzled-7 [KO:K02432]
106832232  FZD1; frizzled-1 [KO:K02432]
106836460  FZD2; frizzled-2 [KO:K02235]
106832528  FZD3; frizzled-3 isoform X1 [KO:K02329]
106848251  FZD4; frizzled-4 [KO:K02354]
106828163  FZD5; LOW QUALITY PROTEIN: frizzled-5 [KO:K02375]
106823513  FZD8; frizzled-8 [KO:K02375]
106822374  FZD6; frizzled-6 [KO:K02376]
106841840  FZD10; frizzled-10 [KO:K02842]
106837127  FZD9; LOW QUALITY PROTEIN: frizzled-9 [KO:K02842]
106844271  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
106834121  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
106845228  DVL1; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
106844176  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
106834527  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
106844950  FRAT1; LOW QUALITY PROTEIN: proto-oncogene FRAT1 [KO:K03069]
123278957  FRAT2; LOW QUALITY PROTEIN: GSK-3-binding protein FRAT2 [KO:K03096]
106829188  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
106836161  AXIN1; axin-1 isoform X1 [KO:K02157]
106835348  AXIN2; axin-2 isoform X1 [KO:K04385]
106834222  APC2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
106832251  APC; LOW QUALITY PROTEIN: adenomatous polyposis coli protein [KO:K02085]
106828390  CTNNB1; catenin beta-1 [KO:K02105]
106838484  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
106834657  TCF7; transcription factor 7 isoform X1 [KO:K02620]
106838609  TCF7L1; transcription factor 7-like 1 [KO:K04490]
106848101  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
106829814  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
106824829  MYC; myc proto-oncogene protein isoform X3 [KO:K04377]
106844248  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
106835880  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
106829795  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
106824133  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
106826341  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
106828516  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
106834253  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
106841633  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
106838625  SHC4; SHC-transforming protein 4 [KO:K17449]
106830292  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
106825844  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
106839506  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
106824973  HRAS; GTPase HRas isoform X1 [KO:K02833]
106825548  KRAS; GTPase KRas isoform X2 [KO:K07827]
106829397  GTPase KRas-like [KO:K07827]
106835678  NRAS; GTPase NRas [KO:K07828]
106847984  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
106842618  BRAF; serine/threonine-protein kinase B-raf isoform X8 [KO:K04365] [EC:2.7.11.1]
106829345  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
106830991  LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
106840602  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
106832322  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106845632  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
106848262  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106838100  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
106829313  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106836695  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106840141  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
106822593  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
106824993  PIK3R2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
106835457  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
106839597  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106843289  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106836676  MTOR; serine/threonine-protein kinase mTOR isoform X3 [KO:K07203] [EC:2.7.11.1]
106833496  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
106841135  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
106832883  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
106834276  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
106826745  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
106841302  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
106831458  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
106832401  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
106829635  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
106823225  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
106839983  E2F2; transcription factor E2F2 [KO:K09389]
106847694  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
106843812  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
106836714  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
106830938  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
106842924  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
106830994  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
106831216  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
106840608  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
106834799  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
106824765  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
106822455  CDH1; cadherin-1 [KO:K05689]
106839218  CTNNA1; catenin alpha-1 [KO:K05691]
106832269  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
106825265  CTNNA3; catenin alpha-3 [KO:K05691]
106826369  junction plakoglobin [KO:K10056]
106840178  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
106829287  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
106836975  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
106838575  FGF7; fibroblast growth factor 7 [KO:K04358]
106831535  FGF6; fibroblast growth factor 6 [KO:K04358]
106847700  FGF17; fibroblast growth factor 17 isoform X3 [KO:K04358]
106828064  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
106834247  FGF22; fibroblast growth factor 22 isoform X2 [KO:K04358]
106828264  FGF20; fibroblast growth factor 20 [KO:K04358]
106844246  FGF4; LOW QUALITY PROTEIN: fibroblast growth factor 4 [KO:K04358]
106844254  FGF3; fibroblast growth factor 3 [KO:K04358]
106846929  FGF16; fibroblast growth factor 16 [KO:K04358]
106837360  FGF18; fibroblast growth factor 18 [KO:K04358]
106828887  FGF8; fibroblast growth factor 8 [KO:K04358]
106824930  FGF10; fibroblast growth factor 10 [KO:K04358]
106828556  FGF9; fibroblast growth factor 9 [KO:K04358]
106844255  FGF19; fibroblast growth factor 19 [KO:K22603]
106838258  FGF21; fibroblast growth factor 21 [KO:K22429]
106831440  FGF23; LOW QUALITY PROTEIN: fibroblast growth factor 23 [KO:K22428]
106846935  FGFR2; fibroblast growth factor receptor 2 isoform X6 [KO:K05093] [EC:2.7.10.1]
106829157  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
eai04010  MAPK signaling pathway
eai04110  Cell cycle
eai04115  p53 signaling pathway
eai04151  PI3K-Akt signaling pathway
eai04310  Wnt signaling pathway
eai04350  TGF-beta signaling pathway
eai04520  Adherens junction
KO pathway
ko05226   
LinkDB

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