KEGG   PATHWAY: pyu05226
Entry
pyu05226                    Pathway                                
Name
Gastric cancer - Herpailurus yagouaroundi (jaguarundi)
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
pyu05226  Gastric cancer
pyu05226

Disease
H00018  Gastric cancer
Organism
Herpailurus yagouaroundi (jaguarundi) [GN:pyu]
Gene
121009705  CDH1; cadherin-1 [KO:K05689]
121010702  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
121010770  CTNNA1; catenin alpha-1 [KO:K05691]
121010888  WNT8A; protein Wnt-8a [KO:K00714]
121010979  FGF18; fibroblast growth factor 18 [KO:K04358]
121011002  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
121011326  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
121011444  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121011897  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
121012039  E2F1; transcription factor E2F1 [KO:K17454]
121012642  CDX2; homeobox protein CDX-2 [KO:K22234]
121012732  FGF9; fibroblast growth factor 9 [KO:K04358]
121012950  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
121013551  SHC3; SHC-transforming protein 3 [KO:K17448]
121013741  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
121014378  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
121014548  FZD8; frizzled-8 [KO:K02375]
121014969  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121015111  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121015318  AXIN2; axin-2 [KO:K04385]
121015654  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
121015982  TP53; cellular tumor antigen p53 [KO:K04451]
121016029  DVL2; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
121016402  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
121016685  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
121016686  WNT3A; protein Wnt-3a [KO:K00312]
121016831  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
121017018  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
121017718  FZD9; frizzled-9 [KO:K02842]
121017912  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
121018482  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
121018739  FGF21; fibroblast growth factor 21 [KO:K22429]
121018751  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
121019071  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
121019121  TCF7L1; transcription factor 7-like 1 [KO:K04490]
121019187  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
121019790  AXIN1; axin-1 isoform X1 [KO:K02157]
121020143  WNT3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
121020160  WNT9B; protein Wnt-9b [KO:K01064]
121020536  E2F3; transcription factor E2F3 [KO:K06620]
121020585  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121020839  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
121020862  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
121021042  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
121021222  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
121021383  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
121021432  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
121021465  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
121021881  FGF22; fibroblast growth factor 22 [KO:K04358]
121021890  SHC2; SHC-transforming protein 2 [KO:K17447]
121021952  FGF23; fibroblast growth factor 23 [KO:K22428]
121021990  FGF6; fibroblast growth factor 6 [KO:K04358]
121022123  WNT5B; protein Wnt-5b [KO:K00444]
121022226  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121022826  HRAS; GTPase HRas isoform X1 [KO:K02833]
121022836  WNT4; protein Wnt-4 [KO:K00408]
121023018  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121023030  E2F2; transcription factor E2F2 [KO:K09389]
121023683  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
121023741  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
121023744  FGF19; fibroblast growth factor 19 [KO:K22603]
121023745  FGF4; fibroblast growth factor 4 [KO:K04358]
121023852  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
121024259  FZD10; frizzled-10 [KO:K02842]
121024563  [KO:K11988]
121024748  FZD3; frizzled-3 isoform X1 [KO:K02329]
121025344  FGF16; fibroblast growth factor 16 [KO:K04358]
121026094  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
121027050  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
121027286  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
121027695  WNT2B; protein Wnt-2b [KO:K00182]
121027738  NRAS; GTPase NRas [KO:K07828]
121027800  REG4; regenerating islet-derived protein 4 [KO:K22244]
121027988  FZD1; frizzled-1 [KO:K02432]
121028241  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
121028423  WNT16; protein Wnt-16 [KO:K01558]
121028442  WNT2; protein Wnt-2 [KO:K00182]
121028446  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
121028771  ABCB1; ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
121028796  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
121029177  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
121029271  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
121029294  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
121029363  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
121030066  FGF2; fibroblast growth factor 2 isoform X1 [KO:K18497]
121030921  FZD7; frizzled-7 isoform X1 [KO:K02432]
121030981  FZD5; frizzled-5 [KO:K02375]
121031012  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
121031082  WNT10A; protein Wnt-10a [KO:K01357]
121031083  WNT6; protein Wnt-6 [KO:K00445]
121031433  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
121031737  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
121032078  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
121032358  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121032687  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
121032920  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
121032957  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
121033449  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
121033506  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
121033562  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
121033582  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
121033707  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
121033733  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
121034018  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121034071  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
121034524  [KO:K04685]
121034732  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
121036286  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
121036689  CTNNA3; catenin alpha-3 [KO:K05691]
121037238  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
121037313  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
121037465  FRAT1; proto-oncogene FRAT1 [KO:K03069]
121037466  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
121037468  WNT8B; protein Wnt-8b [KO:K00714]
121037542  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
121038637  WNT1; proto-oncogene Wnt-1 [KO:K03209]
121038640  WNT10B; protein Wnt-10b [KO:K01357]
121038809  KRAS; GTPase KRas isoform X1 [KO:K07827]
121038909  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
121038918  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
121039303  WNT11; protein Wnt-11 [KO:K01384]
121039382  FZD4; frizzled-4 isoform X1 [KO:K02354]
121039893  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
121039962  FGF20; fibroblast growth factor 20 [KO:K04358]
121040175  WNT7B; protein Wnt-7b [KO:K00572]
121040954  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
121041205  WNT7A; protein Wnt-7a [KO:K00572]
121041241  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121041673  SHC4; SHC-transforming protein 4 [KO:K17449]
121041681  FGF7; fibroblast growth factor 7 isoform X1 [KO:K04358]
121041863  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
121041878  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
121042092  TERT; LOW QUALITY PROTEIN: telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
121042709  CDH17; cadherin-17 isoform X1 [KO:K06811]
121042720  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
121042823  FZD6; frizzled-6 [KO:K02376]
121042977  MYC; myc proto-oncogene protein [KO:K04377]
121043455  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
121044367  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
121044420  FGF10; fibroblast growth factor 10 [KO:K04358]
121044690  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
121044888  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
121044914  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
121044997  [KO:K10056]
121045102  FZD2; frizzled-2 [KO:K02235]
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
pyu04010  MAPK signaling pathway
pyu04110  Cell cycle
pyu04115  p53 signaling pathway
pyu04151  PI3K-Akt signaling pathway
pyu04310  Wnt signaling pathway
pyu04350  TGF-beta signaling pathway
pyu04520  Adherens junction
KO pathway
ko05226   

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