KEGG   PATHWAY: clud05226
Entry
clud05226                   Pathway                                
Name
Gastric cancer - Canis lupus dingo (dingo)
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
clud05226  Gastric cancer
clud05226

Organism
Canis lupus dingo (dingo) [GN:clud]
Gene
112670097  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
112663246  MUC2; LOW QUALITY PROTEIN: mucin-2 [KO:K10955]
112650784  CDH17; cadherin-17 [KO:K06811]
112664087  regenerating islet-derived protein 4-like [KO:K22244]
112664101  regenerating islet-derived protein 4-like [KO:K22244]
112674990  ABCB1; ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
112663058  SHH; sonic hedgehog protein [KO:K11988]
112647438  TP53; cellular tumor antigen p53 [KO:K04451]
112641497  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
112644859  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112641088  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112666236  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
112645177  BAX; apoptosis regulator BAX [KO:K02159]
112641425  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
112663311  DDB2; DNA damage-binding protein 2 isoform X2 [KO:K10140]
112653354  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
112668632  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
112677388  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
112641393  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
112643074  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
112678279  WNT1; proto-oncogene Wnt-1 isoform X1 [KO:K03209]
112670801  WNT2; protein Wnt-2 isoform X2 [KO:K00182]
112663902  WNT2B; protein Wnt-2b [KO:K00182]
112652965  WNT3; proto-oncogene Wnt-3 [KO:K00312]
112665303  WNT3A; protein Wnt-3a [KO:K00312]
112660019  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
112668992  WNT5B; protein Wnt-5b [KO:K00444]
112665934  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
112656503  WNT6; protein Wnt-6 [KO:K00445]
112660989  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
112666027  WNT7B; protein Wnt-7b isoform X5 [KO:K00572]
112672198  WNT8B; protein Wnt-8b [KO:K00714]
112650067  WNT8A; protein Wnt-8a isoform X1 [KO:K00714]
112652984  WNT9B; protein Wnt-9b [KO:K01064]
112665302  WNT9A; protein Wnt-9a [KO:K01064]
112656502  WNT10A; protein Wnt-10a [KO:K01357]
112678278  WNT10B; protein Wnt-10b isoform X2 [KO:K01357]
112642157  WNT11; protein Wnt-11 [KO:K01384]
112678075  WNT16; protein Wnt-16 [KO:K01558]
112674955  FZD1; frizzled-1 [KO:K02432]
112656639  FZD7; frizzled-7 [KO:K02432]
112655297  FZD2; frizzled-2 [KO:K02235]
112669675  FZD3; frizzled-3 isoform X1 [KO:K02329]
112642049  FZD4; frizzled-4 [KO:K02354]
112678994  FZD8; frizzled-8 [KO:K02375]
112656460  FZD5; frizzled-5 [KO:K02375]
112662097  FZD6; frizzled-6 isoform X1 [KO:K02376]
112646159  FZD9; frizzled-9 [KO:K02842]
112676414  FZD10; frizzled-10 [KO:K02842]
112659229  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
112665398  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
112647012  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
112647486  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
112662657  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X2 [KO:K02353]
112672132  proto-oncogene FRAT1-like [KO:K03069]
112672133  LOW QUALITY PROTEIN: GSK-3-binding protein FRAT2-like [KO:K03096]
112677588  GSK3B; glycogen synthase kinase-3 beta isoform X3 [KO:K03083] [EC:2.7.11.26]
112640639  AXIN1; axin-1 isoform X2 [KO:K02157]
112652925  AXIN2; axin-2 isoform X1 [KO:K04385]
112653650  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
112666189  APC2; adenomatous polyposis coli protein 2 isoform X3 [KO:K02085]
112668716  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
112651839  CSNK1A1; casein kinase I isoform X3 [KO:K08957] [EC:2.7.11.1]
112650538  TCF7; transcription factor 7 isoform X3 [KO:K02620]
112664304  TCF7L1; transcription factor 7-like 1 [KO:K04490]
112672346  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
112671621  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
112662261  MYC; myc proto-oncogene protein [KO:K04377]
112663184  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
112662671  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
112671646  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
112661500  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
112655065  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
112648956  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
112666141  SHC2; SHC-transforming protein 2 isoform X3 [KO:K17447]
112644865  SHC3; SHC-transforming protein 3 [KO:K17448]
112675960  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
112672798  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
112657995  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
112664493  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
112663536  HRAS; GTPase HRas isoform X1 [KO:K02833]
112665533  KRAS; GTPase KRas isoform X1 [KO:K07827]
112664166  NRAS; GTPase NRas [KO:K07828]
112673245  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
112650991  BRAF; serine/threonine-protein kinase B-raf isoform X5 [KO:K04365] [EC:2.7.11.1]
112661394  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112675721  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112666294  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
112640050  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
112677029  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112669083  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
112646871  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X5 [KO:K00922] [EC:2.7.1.153]
112661215  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112662621  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112666735  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112660199  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112642563  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
112658031  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112648737  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112645463  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112678102  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
112655510  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
112659290  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
112644027  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
112668776  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
112665406  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
112678040  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
112645606  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
112650816  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
112678896  RB1; retinoblastoma-associated protein isoform X2 [KO:K06618]
112673817  E2F1; transcription factor E2F1 isoform X2 [KO:K17454]
112660192  E2F2; transcription factor E2F2 [KO:K09389]
112657478  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
112645426  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
112643136  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
112657820  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
112649823  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
112668662  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
112647773  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
112675712  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
112644105  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
112649891  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
112646539  CDH1; cadherin-1 [KO:K05689]
112646860  cadherin-1-like [KO:K05689]
112650087  CTNNA1; catenin alpha-1 [KO:K05691]
112664282  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
112652001  CTNNA3; catenin alpha-3 isoform X1 [KO:K05691]
112655046  junction plakoglobin [KO:K10056]
112661349  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
112670796  MET; hepatocyte growth factor receptor isoform X3 [KO:K05099] [EC:2.7.10.1]
112659082  FGF1; fibroblast growth factor 1 isoform X2 [KO:K18496]
112642713  FGF2; fibroblast growth factor 2 isoform X2 [KO:K18497]
112646589  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
112669052  FGF6; fibroblast growth factor 6 [KO:K04358]
112669538  FGF9; fibroblast growth factor 9 [KO:K04358]
112669777  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
112671881  FGF16; fibroblast growth factor 16 [KO:K04358]
112672591  FGF8; fibroblast growth factor 8 [KO:K04358]
112663090  FGF3; fibroblast growth factor 3 [KO:K04358]
112663188  FGF4; fibroblast growth factor 4 [KO:K04358]
112651446  FGF10; fibroblast growth factor 10 [KO:K04358]
112651532  FGF18; fibroblast growth factor 18 isoform X1 [KO:K04358]
112675596  FGF20; fibroblast growth factor 20 [KO:K04358]
112666152  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
112675956  FGF7; fibroblast growth factor 7 [KO:K04358]
112663089  FGF19; fibroblast growth factor 19 [KO:K22603]
112645189  FGF21; fibroblast growth factor 21 [KO:K22429]
112669051  FGF23; fibroblast growth factor 23 [KO:K22428]
112672433  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
112669327  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
clud04010  MAPK signaling pathway
clud04110  Cell cycle
clud04115  p53 signaling pathway
clud04151  PI3K-Akt signaling pathway
clud04310  Wnt signaling pathway
clud04350  TGF-beta signaling pathway
clud04520  Adherens junction
KO pathway
ko05226   
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