KEGG   PATHWAY: npo05226
Entry
npo05226                    Pathway                                
Name
Gastric cancer - Nyctereutes procyonoides (raccoon dog)
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
npo05226  Gastric cancer
npo05226

Organism
Nyctereutes procyonoides (raccoon dog) [GN:npo]
Gene
129504648  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
129495720  CDH17; cadherin-17 [KO:K06811]
129501190  regenerating islet-derived protein 4-like [KO:K22244]
129501538  REG4; regenerating islet-derived protein 4 [KO:K22244]
129498291  ABCB1; ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
129516222  SHH; sonic hedgehog protein [KO:K11988]
129497070  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
129512989  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
129500388  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
129519073  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
129521889  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
129501028  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
129513046  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
129499055  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
129521032  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
129506911  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
129510105  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
129512540  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
129515284  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
129517408  WNT1; proto-oncogene Wnt-1 [KO:K03209]
129501220  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
129502893  WNT2; protein Wnt-2 [KO:K00182]
129506798  WNT3; LOW QUALITY PROTEIN: proto-oncogene Wnt-3 [KO:K00312]
129515047  WNT3A; protein Wnt-3a [KO:K00312]
129513678  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
129503341  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
129521805  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
129523023  WNT6; protein Wnt-6 [KO:K00445]
129511925  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
129521980  WNT7A; protein Wnt-7a [KO:K00572]
129494611  WNT8A; protein Wnt-8a [KO:K00714]
129493561  WNT8B; protein Wnt-8b [KO:K00714]
129500703  WNT9B; protein Wnt-9b [KO:K01064]
129514999  WNT9A; protein Wnt-9a [KO:K01064]
129522994  WNT10A; protein Wnt-10a [KO:K01357]
129517200  WNT10B; protein Wnt-10b [KO:K01357]
129506696  WNT11; protein Wnt-11 [KO:K01384]
129502963  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
129498263  FZD1; frizzled-1 [KO:K02432]
129522877  FZD7; frizzled-7 isoform X1 [KO:K02432]
129510346  FZD2; frizzled-2 [KO:K02235]
129493707  FZD3; frizzled-3 [KO:K02329]
129506743  FZD4; frizzled-4 [KO:K02354]
129499073  FZD8; frizzled-8 [KO:K02375]
129522741  FZD5; LOW QUALITY PROTEIN: frizzled-5 [KO:K02375]
129495713  FZD6; frizzled-6 isoform X1 [KO:K02376]
129508175  FZD10; frizzled-10 [KO:K02842]
129519529  FZD9; frizzled-9 [KO:K02842]
129500698  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
129517122  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
129496981  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
129497764  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
129498669  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
129523328  proto-oncogene FRAT1-like [KO:K03069]
129523327  LOW QUALITY PROTEIN: GSK-3-binding protein FRAT2-like [KO:K03096]
129503652  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129519365  AXIN1; axin-1 isoform X1 [KO:K02157]
129507164  AXIN2; axin-2 isoform X1 [KO:K04385]
129519526  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
129521503  APC2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
129506984  CTNNB1; catenin beta-1 [KO:K02105]
129509530  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
129494859  TCF7; transcription factor 7 isoform X1 [KO:K02620]
129510910  TCF7L1; transcription factor 7-like 1 [KO:K04490]
129493862  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
129521205  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
129502657  MYC; myc proto-oncogene protein [KO:K04377]
129502968  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
129498630  TERT; LOW QUALITY PROTEIN: telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
129521218  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
129494118  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
129505762  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
129508769  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
129522289  SHC2; SHC-transforming protein 2 [KO:K17447]
129500459  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
129506392  SHC4; SHC-transforming protein 4 [KO:K17449]
129511906  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
129496132  SOS2; son of sevenless homolog 2 [KO:K03099]
129510881  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
129494224  HRAS; GTPase HRas isoform X1 [KO:K02833]
129505561  KRAS; GTPase KRas isoform X1 [KO:K07827]
129501466  NRAS; GTPase NRas [KO:K07828]
129518309  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
129515848  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
129522592  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129506345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129522322  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129502349  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
129507918  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129519082  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129496789  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129498637  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129507069  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129513452  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129520803  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129522073  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129508823  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129495892  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129499851  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
129517633  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129514778  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129513263  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
129501834  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
129510988  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
129495480  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129514527  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129505236  DNA mismatch repair protein Mlh1-like [KO:K08734]
129507335  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
129517176  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
129511299  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
129501012  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
129495669  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
129497562  G1/S-specific cyclin-E1-like [KO:K06626]
129516428  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
129496621  E2F1; transcription factor E2F1 [KO:K17454]
129514246  E2F2; transcription factor E2F2 [KO:K09389]
129507839  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
129500810  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
129515208  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
129496088  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
129495112  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
129507207  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
129508622  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
129506293  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
129495555  mothers against decapentaplegic homolog 4 [KO:K04501]
129514601  mothers against decapentaplegic homolog 4 [KO:K04501]
129495074  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
129496751  CDH1; cadherin-1 [KO:K05689]
129496858  cadherin-1-like [KO:K05689]
129501541  CTNNA2; catenin alpha-2 [KO:K05691]
129494741  CTNNA1; catenin alpha-1 [KO:K05691]
129499209  CTNNA3; catenin alpha-3 isoform X1 [KO:K05691]
129495798  JUP; junction plakoglobin [KO:K10056]
129494407  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
129502777  MET; LOW QUALITY PROTEIN: hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
129514194  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
129504328  FGF2; fibroblast growth factor 2 [KO:K18497]
129501850  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
129509339  FGF10; fibroblast growth factor 10 [KO:K04358]
129493821  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
129493891  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
129503172  FGF3; fibroblast growth factor 3 [KO:K04358]
129503472  FGF6; fibroblast growth factor 6 isoform X1 [KO:K04358]
129504579  FGF9; fibroblast growth factor 9 [KO:K04358]
129499133  FGF4; LOW QUALITY PROTEIN: fibroblast growth factor 4 [KO:K04358]
129506303  FGF7; fibroblast growth factor 7 isoform X1 [KO:K04358]
129516186  FGF20; fibroblast growth factor 20 [KO:K04358]
129509565  FGF18; fibroblast growth factor 18 [KO:K04358]
129518363  FGF16; fibroblast growth factor 16 [KO:K04358]
129521996  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
129503174  FGF19; fibroblast growth factor 19 [KO:K22603]
129499873  FGF21; fibroblast growth factor 21 [KO:K22429]
129503368  FGF23; fibroblast growth factor 23 [KO:K22428]
129523284  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
129504382  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
npo04010  MAPK signaling pathway
npo04110  Cell cycle
npo04115  p53 signaling pathway
npo04151  PI3K-Akt signaling pathway
npo04310  Wnt signaling pathway
npo04350  TGF-beta signaling pathway
npo04520  Adherens junction
KO pathway
ko05226   
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