KEGG   PATHWAY: ray05226
Entry
ray05226                    Pathway                                
Name
Gastric cancer - Rousettus aegyptiacus (Egyptian rousette)
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
ray05226  Gastric cancer
ray05226

Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107516497  CDX2; LOW QUALITY PROTEIN: homeobox protein CDX-2 [KO:K22234]
107504064  LOW QUALITY PROTEIN: mucin-2-like [KO:K10955]
107502367  CDH17; cadherin-17 [KO:K06811]
107514343  REG4; regenerating islet-derived protein 4 isoform X1 [KO:K22244]
107512458  ABCB1; multidrug resistance protein 1 isoform X1 [KO:K05658] [EC:7.6.2.2]
107518868  SHH; LOW QUALITY PROTEIN: sonic hedgehog protein [KO:K11988]
107515689  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
107514682  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
107520573  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
107520147  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
107499083  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
107498831  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
107511968  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
107511851  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
107506450  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
107500055  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
107502027  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
107511984  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
107512732  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
107514294  WNT1; proto-oncogene Wnt-1 [KO:K03209]
107505364  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
107499803  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
107509667  WNT3A; protein Wnt-3a [KO:K00312]
107508173  WNT3; proto-oncogene Wnt-3 [KO:K00312]
107513057  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
107503411  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
107500582  WNT5B; protein Wnt-5b [KO:K00444]
107516780  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
107505517  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
107502411  WNT7A; protein Wnt-7a [KO:K00572]
107518710  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
107499773  WNT8B; protein Wnt-8b [KO:K00714]
107509675  WNT9A; protein Wnt-9a [KO:K01064]
107508172  WNT9B; protein Wnt-9b [KO:K01064]
107514289  WNT10B; protein Wnt-10b [KO:K01357]
107516694  WNT10A; protein Wnt-10a [KO:K01357]
107519202  WNT11; LOW QUALITY PROTEIN: protein Wnt-11 [KO:K01384]
107500238  WNT16; protein Wnt-16 [KO:K01558]
107519374  FZD7; frizzled-7 [KO:K02432]
107500880  FZD1; frizzled-1 [KO:K02432]
107508108  FZD2; frizzled-2 [KO:K02235]
107510778  FZD3; frizzled-3 isoform X1 [KO:K02329]
107518567  FZD4; frizzled-4 [KO:K02354]
107505121  FZD8; frizzled-8 [KO:K02375]
107505167  FZD5; frizzled-5 [KO:K02375]
107512212  FZD6; frizzled-6 [KO:K02376]
107511767  FZD9; frizzled-9 [KO:K02842]
107511534  FZD10; frizzled-10 [KO:K02842]
107503467  LRP5; LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 5 [KO:K03068]
107516546  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
107507013  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
107509513  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
107510646  DVL1; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
107520415  FRAT1; proto-oncogene FRAT1 [KO:K03069]
107520416  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
107517741  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107506131  AXIN1; axin-1 isoform X1 [KO:K02157]
107510301  AXIN2; axin-2 isoform X1 [KO:K04385]
107500934  APC2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
107512008  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
107519993  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
107513552  CSNK1A1; casein kinase I isoform alpha isoform X1 [KO:K08957] [EC:2.7.11.1]
107506797  TCF7; transcription factor 7 isoform X1 [KO:K02620]
107506285  TCF7L1; transcription factor 7-like 1 [KO:K04490]
107511705  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
107511497  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
107506202  MYC; myc proto-oncogene protein [KO:K04377]
107503391  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
107499970  TERT; LOW QUALITY PROTEIN: telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
107508819  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
107498193  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
107520699  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
107505474  SHC1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
107512423  LOW QUALITY PROTEIN: SHC-transforming protein 1-like [KO:K06279]
107500961  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
107504308  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
107519965  SHC4; SHC-transforming protein 4 [KO:K17449]
107503781  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
107519446  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107511436  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
107507127  HRAS; GTPase HRas isoform X1 [KO:K02833]
107497434  KRAS; GTPase KRas isoform X1 [KO:K07827]
107499847  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
107509353  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
107504052  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
107519729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
107508942  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
107510634  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107520152  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107517828  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107513958  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107521668  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
107517899  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
107498704  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107513978  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107521783  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107498395  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107513109  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
107503682  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
107510136  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
107503915  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
107499602  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
107516566  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
107521282  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
107502556  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
107515884  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
107520925  RB1; retinoblastoma-associated protein [KO:K06618]
107519491  E2F1; transcription factor E2F1 [KO:K17454]
107501037  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
107501692  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
107505490  TGFB1; transforming growth factor beta-1 [KO:K13375]
107520844  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
107498899  TGFB3; transforming growth factor beta-3 [KO:K13377]
107500589  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
107508791  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
107512663  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
107508935  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
107512852  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
107506721  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
107520648  CDH1; LOW QUALITY PROTEIN: cadherin-1 [KO:K05689]
107518703  CTNNA1; catenin alpha-1 [KO:K05691]
107499343  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
107510357  CTNNA3; catenin alpha-3 [KO:K05691]
107513800  JUP; LOW QUALITY PROTEIN: junction plakoglobin [KO:K10056]
107501285  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
107497465  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
107500865  FGF1; fibroblast growth factor 1 [KO:K18496]
107518501  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
107507115  FGF16; fibroblast growth factor 16 [KO:K04358]
107503931  FGF3; fibroblast growth factor 3 [KO:K04358]
107503977  FGF4; LOW QUALITY PROTEIN: fibroblast growth factor 4 [KO:K04358]
107511020  FGF18; fibroblast growth factor 18 [KO:K04358]
107514447  FGF9; fibroblast growth factor 9 [KO:K04358]
107502706  FGF20; fibroblast growth factor 20 [KO:K04358]
107513447  FGF6; fibroblast growth factor 6 [KO:K04358]
107516440  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
107509200  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
107518965  FGF10; fibroblast growth factor 10 [KO:K04358]
107500922  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
107497786  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
107501960  FGF7; LOW QUALITY PROTEIN: fibroblast growth factor 7 [KO:K04358]
107498854  FGF21; fibroblast growth factor 21 [KO:K22429]
107513448  FGF23; fibroblast growth factor 23 [KO:K22428]
107512997  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
107499274  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
ray04010  MAPK signaling pathway
ray04110  Cell cycle
ray04115  p53 signaling pathway
ray04151  PI3K-Akt signaling pathway
ray04310  Wnt signaling pathway
ray04350  TGF-beta signaling pathway
ray04520  Adherens junction
KO pathway
ko05226   
LinkDB

DBGET integrated database retrieval system