KEGG   PATHWAY: vvp05226
Entry
vvp05226                    Pathway                                
Name
Gastric cancer - Vulpes vulpes (red fox)
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
vvp05226  Gastric cancer
vvp05226

Organism
Vulpes vulpes (red fox) [GN:vvp]
Gene
112918526  CDX2; homeobox protein CDX-2 [KO:K22234]
112923992  MUC2; mucin-2 [KO:K10955]
112932107  CDH17; cadherin-17 [KO:K06811]
112912526  regenerating islet-derived protein 4-like [KO:K22244]
112912048  REG4; regenerating islet-derived protein 4 [KO:K22244]
112935070  ABCB1; multidrug resistance protein 1 [KO:K05658] [EC:7.6.2.2]
112924853  TP53; cellular tumor antigen p53 [KO:K04451]
112913942  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
112908633  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112910526  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112935608  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
112931372  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
112913897  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
112924073  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
112919752  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
112925585  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
112906873  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
112913873  RXRB; retinoic acid receptor RXR-beta [KO:K08525]
112914313  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
112921098  WNT1; proto-oncogene Wnt-1 isoform X1 [KO:K03209]
112907938  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
112929869  WNT2; protein Wnt-2 [KO:K00182]
112911970  WNT3A; protein Wnt-3a [KO:K00312]
112920633  WNT3; proto-oncogene Wnt-3 [KO:K00312]
112929848  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
112909974  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
112917420  WNT5B; protein Wnt-5b [KO:K00444]
112922542  WNT6; protein Wnt-6 [KO:K00445]
112914456  WNT7A; protein Wnt-7a [KO:K00572]
112935842  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
112914893  WNT8B; protein Wnt-8b [KO:K00714]
112921902  WNT8A; protein Wnt-8a [KO:K00714]
112911976  WNT9A; protein Wnt-9a [KO:K01064]
112920632  WNT9B; protein Wnt-9b [KO:K01064]
112922477  WNT10A; protein Wnt-10a [KO:K01357]
112921097  WNT10B; protein Wnt-10b [KO:K01357]
112928634  WNT11; protein Wnt-11 [KO:K01384]
112910612  WNT16; protein Wnt-16 [KO:K01558]
112923874  FZD1; frizzled-1 [KO:K02432]
112922796  FZD7; frizzled-7 [KO:K02432]
112910678  FZD2; frizzled-2 [KO:K02235]
112926772  FZD3; frizzled-3 [KO:K02329]
112932336  FZD4; frizzled-4 [KO:K02354]
112922465  FZD5; frizzled-5 [KO:K02375]
112921504  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
112916996  FZD6; frizzled-6 [KO:K02376]
112933856  FZD10; frizzled-10 [KO:K02842]
112935737  FZD9; frizzled-9 [KO:K02842]
112917281  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
112924019  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
112926256  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
112924817  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
112926150  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
112908489  FRAT1; proto-oncogene FRAT1 [KO:K03069]
112909220  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
112913469  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
112909128  AXIN1; axin-1 isoform X1 [KO:K02157]
112920730  AXIN2; axin-2 isoform X1 [KO:K04385]
112935524  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
112915436  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
112921625  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
112927455  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
112917059  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
112916685  TCF7L1; transcription factor 7-like 1 [KO:K04490]
112916157  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
112934208  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
112915979  MYC; myc proto-oncogene protein [KO:K04377]
112924157  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
112935454  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
112934223  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
112925820  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
112917778  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
112918897  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
112935467  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
112908627  SHC3; SHC-transforming protein 3 [KO:K17448]
112920045  SHC4; SHC-transforming protein 4 [KO:K17449]
112920790  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
112921310  SOS2; son of sevenless homolog 2 [KO:K03099]
112935267  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
112914428  HRAS; GTPase HRas isoform X1 [KO:K02833]
112917213  KRAS; GTPase KRas isoform X1 [KO:K07827]
112916766  NRAS; GTPase NRas [KO:K07828]
112907269  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
112907060  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
112933694  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112935545  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
112929340  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112907501  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112924665  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112926217  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112934961  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112914774  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
112913170  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112935820  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112928376  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112930303  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112923528  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112929738  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
112917940  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
112924182  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
112919203  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
112921667  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
112917274  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
112922404  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
112931227  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
112928464  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
112933932  RB1; retinoblastoma-associated protein [KO:K06618]
112928157  E2F1; transcription factor E2F1 [KO:K17454]
112930133  E2F2; transcription factor E2F2 [KO:K09389]
112920427  E2F3; transcription factor E2F3 [KO:K06620]
112928349  TGFB1; transforming growth factor beta-1 isoform X1 [KO:K13375]
112914338  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
112927298  TGFB3; transforming growth factor beta-3 [KO:K13377]
112930794  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
112921591  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
112918856  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
112929830  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
112919269  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
112911637  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
112929524  CDH1; cadherin-1 [KO:K05689]
112924654  cadherin-1-like [KO:K05689]
112916691  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
112921969  CTNNA1; catenin alpha-1 [KO:K05691]
112910756  JUP; junction plakoglobin [KO:K10056]
112925397  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
112929871  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
112934748  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
112933647  FGF2; fibroblast growth factor 2 [KO:K18497]
112926828  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
112928529  FGF18; fibroblast growth factor 18 [KO:K04358]
112919573  FGF5; fibroblast growth factor 5 [KO:K04358]
112913369  FGF8; fibroblast growth factor 8 [KO:K04358]
112909183  FGF16; fibroblast growth factor 16 [KO:K04358]
112924012  FGF3; fibroblast growth factor 3 [KO:K04358]
112924013  FGF4; fibroblast growth factor 4 [KO:K04358]
112917377  FGF6; fibroblast growth factor 6 [KO:K04358]
112918609  FGF9; fibroblast growth factor 9 [KO:K04358]
112920051  FGF7; fibroblast growth factor 7 [KO:K04358]
112908925  FGF20; fibroblast growth factor 20 [KO:K04358]
112933766  FGF10; fibroblast growth factor 10 [KO:K04358]
112924014  FGF19; fibroblast growth factor 19 [KO:K22603]
112931222  FGF21; fibroblast growth factor 21 [KO:K22429]
112917521  FGF23; fibroblast growth factor 23 [KO:K22428]
112916723  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
112911650  GAB1; GRB2-associated-binding protein 1 [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
vvp04010  MAPK signaling pathway
vvp04110  Cell cycle
vvp04115  p53 signaling pathway
vvp04151  PI3K-Akt signaling pathway
vvp04310  Wnt signaling pathway
vvp04350  TGF-beta signaling pathway
vvp04520  Adherens junction
KO pathway
ko05226   
LinkDB

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