KEGG   PATHWAY: oas05226
Entry
oas05226                    Pathway                                
Name
Gastric cancer - Ovis aries (sheep)
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
oas05226  Gastric cancer
oas05226

Organism
Ovis aries (sheep) [GN:oas]
Gene
101112831  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
780488  MUC2; mucin-2 [KO:K10955]
101111295  CDH17; cadherin-17 isoform X1 [KO:K06811]
101111843  REG4; regenerating islet-derived protein 4 [KO:K22244]
443367  ABCB1; multidrug resistance protein 1 [KO:K05658] [EC:7.6.2.2]
101112460  ATP-dependent translocase ABCB1-like isoform X1 [KO:K05658] [EC:7.6.2.2]
101121256  ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
101117666  SHH; sonic hedgehog protein [KO:K11988]
443421  TP53; cellular tumor antigen p53 [KO:K04451]
100302083  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101115240  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100885762  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101120573  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
443059  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
443062  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
101116344  DDB2; DNA damage-binding protein 2 isoform X2 [KO:K10140]
101109360  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
101122663  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
114113852  RXRA; retinoic acid receptor RXR-alpha isoform X2 [KO:K08524]
101110798  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
101111845  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
101103389  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101116782  WNT2B; protein Wnt-2b [KO:K00182]
100126577  WNT2; protein Wnt-2 precursor [KO:K00182]
101120096  WNT3; proto-oncogene Wnt-3 [KO:K00312]
101123374  WNT3A; protein Wnt-3a [KO:K00312]
101122423  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
101121415  WNT5B; protein Wnt-5b isoform X2 [KO:K00444]
101109745  WNT5A; protein Wnt-5a [KO:K00444]
101111785  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
101109531  WNT7B; protein Wnt-7b isoform X2 [KO:K00572]
114109341  WNT7A; protein Wnt-7a [KO:K00572]
101121814  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
101108044  WNT8A; protein Wnt-8a [KO:K00714]
121820714  WNT9B; protein Wnt-9b [KO:K01064]
101102060  WNT9A; protein Wnt-9a [KO:K01064]
101102299  WNT10B; protein Wnt-10b [KO:K01357]
101113129  WNT10A; protein Wnt-10a [KO:K01357]
101111048  WNT11; protein Wnt-11 [KO:K01384]
101103229  WNT16; protein Wnt-16 [KO:K01558]
101103546  FZD7; frizzled-7 [KO:K02432]
101112309  FZD1; frizzled-1 [KO:K02432]
780481  FZD2; frizzled-2 [KO:K02235]
780482  FZD3; frizzled-3 isoform X1 [KO:K02329]
114110622  liprin-alpha-1-like [KO:K02329]
101101932  FZD4; frizzled-4 [KO:K02354]
101118762  FZD5; frizzled-5 [KO:K02375]
114117561  FZD8; frizzled-8 [KO:K02375]
101122197  FZD6; frizzled-6 [KO:K02376]
101114236  FZD9; frizzled-9 [KO:K02842]
101118991  FZD10; frizzled-10 [KO:K02842]
101112971  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
101113714  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
101117599  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X2 [KO:K02353]
101104259  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
101107926  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X2 [KO:K02353]
105609583  FRAT1; proto-oncogene FRAT1 [KO:K03069]
101108269  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
100169938  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
101122656  AXIN1; axin-1 isoform X1 [KO:K02157]
101109815  AXIN2; axin-2 isoform X1 [KO:K04385]
101115458  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
101104664  APC; adenomatous polyposis coli protein isoform X3 [KO:K02085]
100294600  CTNNB1; catenin beta-1 [KO:K02105]
101115603  casein kinase I [KO:K08957] [EC:2.7.11.1]
101116124  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
101120241  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
105605648  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
114111272  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
101101980  TCF7; transcription factor 7 isoform X6 [KO:K02620]
100913162  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
101118068  TCF7L2; transcription factor 7-like 2 isoform X19 [KO:K04491]
780521  LEF1; lymphoid enhancer-binding factor 1 isoform X8 [KO:K04492]
443447  MYC; myc proto-oncogene protein [KO:K04377]
100144763  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100126866  TERT; telomerase reverse transcriptase isoform X1 [KO:K11126] [EC:2.7.7.49]
780479  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
780519  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X2 [KO:K05083] [EC:2.7.10.1]
101113548  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
101113847  SHC2; SHC-transforming protein 2 [KO:K17447]
101107936  SHC3; SHC-transforming protein 3 [KO:K17448]
101110241  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
101109893  GRB2; growth factor receptor-bound protein 2 isoform X5 [KO:K04364]
114110058  growth factor receptor-bound protein 2 [KO:K04364]
101118865  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
101102732  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101104357  HRAS; GTPase HRas isoform X1 [KO:K02833]
114114919  GTPase HRas-like [KO:K02833]
101114005  KRAS; GTPase KRas isoform X1 [KO:K07827]
101102438  NRAS; GTPase NRas [KO:K07828]
100305131  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101107438  BRAF; serine/threonine-protein kinase B-raf isoform X3 [KO:K04365] [EC:2.7.11.1]
101103190  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
101123635  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
101113846  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101115485  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
101123008  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101109759  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101110015  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101117348  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
101123247  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101111546  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101121455  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
101118462  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101119242  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100294652  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100271659  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101107371  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101109574  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
101119602  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
101108344  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
100127219  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100216433  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
101109811  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
101107124  CCNE1; G1/S-specific cyclin-E1 isoform X2 [KO:K06626]
100144755  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
101117526  E2F1; transcription factor E2F1 [KO:K17454]
105606975  E2F2; transcription factor E2F2 [KO:K09389]
101121809  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
443417  TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
554322  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
554323  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
554326  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
494191  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
101114231  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
443169  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
443171  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101107164  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101119747  CDH1; cadherin-1 [KO:K05689]
101123346  CTNNA3; catenin alpha-3 isoform X5 [KO:K05691]
101112313  CTNNA1; catenin alpha-1 isoform X3 [KO:K05691]
101121501  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
114110421  LOW QUALITY PROTEIN: catenin alpha-1-like [KO:K05691]
101119486  JUP; junction plakoglobin isoform X3 [KO:K10056]
114110852  junction plakoglobin-like [KO:K10056]
443075  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
443076  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
101109353  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
443306  FGF2; fibroblast growth factor 2 precursor [KO:K18497]
101116844  FGF9; fibroblast growth factor 9 [KO:K04358]
101116004  FGF4; fibroblast growth factor 4 [KO:K04358]
443074  FGF10; fibroblast growth factor 10 precursor [KO:K04358]
101113716  FGF8; fibroblast growth factor 8 [KO:K04358]
101104968  FGF16; fibroblast growth factor 16 [KO:K04358]
443095  FGF7; fibroblast growth factor 7 [KO:K04358]
100642180  FGF5; fibroblast growth factor 5 isoform 1 precursor [KO:K04358]
101121489  FGF20; fibroblast growth factor 20 [KO:K04358]
101118502  FGF17; fibroblast growth factor 17 isoform X2 [KO:K04358]
101114608  FGF22; fibroblast growth factor 22 isoform X2 [KO:K04358]
101116719  FGF6; fibroblast growth factor 6 [KO:K04358]
780460  FGF18; fibroblast growth factor 18 [KO:K04358]
101116269  FGF3; fibroblast growth factor 3 isoform X1 [KO:K04358]
101115744  FGF19; fibroblast growth factor 19 [KO:K22603]
101108510  FGF21; fibroblast growth factor 21 [KO:K22429]
101112475  FGF23; fibroblast growth factor 23 [KO:K22428]
443548  FGFR2; fibroblast growth factor receptor 2 isoform X3 [KO:K05093] [EC:2.7.10.1]
101112165  GAB1; GRB2-associated-binding protein 1 isoform X4 [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
oas04010  MAPK signaling pathway
oas04110  Cell cycle
oas04115  p53 signaling pathway
oas04151  PI3K-Akt signaling pathway
oas04310  Wnt signaling pathway
oas04350  TGF-beta signaling pathway
oas04520  Adherens junction
KO pathway
ko05226   
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