KEGG   PATHWAY: pteh05226
Entry
pteh05226                   Pathway                                
Name
Gastric cancer - Piliocolobus tephrosceles (Ugandan red Colobus)
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
pteh05226  Gastric cancer
pteh05226

Organism
Piliocolobus tephrosceles (Ugandan red Colobus) [GN:pteh]
Gene
111540394  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
111549686  CDH17; cadherin-17 [KO:K06811]
111549571  REG4; regenerating islet-derived protein 4 isoform X1 [KO:K22244]
111552430  ABCB1; ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
111551526  SHH; sonic hedgehog protein [KO:K11988]
111527100  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
111542983  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
111541101  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
111528537  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
111520681  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
111520083  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
111542928  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
111544893  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
111539938  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
111539463  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
111523996  photoreceptor-specific nuclear receptor-like [KO:K08524]
111534772  retinoic acid receptor RXR-alpha [KO:K08524]
111542907  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
111539204  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
111542045  WNT1; proto-oncogene Wnt-1 [KO:K03209]
111553419  WNT2; protein Wnt-2 [KO:K00182]
111556053  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
111528374  WNT3; proto-oncogene Wnt-3 [KO:K00312]
111536986  WNT3A; protein Wnt-3a [KO:K00312]
111547777  WNT4; protein Wnt-4 [KO:K00408]
111520300  WNT5B; protein Wnt-5b [KO:K00444]
111524378  WNT5A; protein Wnt-5a [KO:K00444]
111546073  WNT6; protein Wnt-6 [KO:K00445]
111529314  WNT7A; protein Wnt-7a [KO:K00572]
111549155  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
111538807  WNT8B; protein Wnt-8b [KO:K00714]
111527470  WNT8A; protein Wnt-8a isoform X1 [KO:K00714]
111528375  WNT9B; protein Wnt-9b isoform X1 [KO:K01064]
111537061  WNT9A; protein Wnt-9a [KO:K01064]
111542044  WNT10B; protein Wnt-10b [KO:K01357]
111546079  WNT10A; protein Wnt-10a [KO:K01357]
111540697  WNT11; protein Wnt-11 [KO:K01384]
111550237  protein Wnt-16 [KO:K01558]
113224821  protein Wnt-16 [KO:K01558]
111552479  FZD1; frizzled-1 [KO:K02432]
111545811  FZD7; frizzled-7 [KO:K02432]
111525827  FZD2; frizzled-2 [KO:K02235]
111545779  FZD3; frizzled-3 [KO:K02329]
111540757  FZD4; frizzled-4 [KO:K02354]
111546690  FZD8; frizzled-8 [KO:K02375]
111547737  FZD5; frizzled-5 [KO:K02375]
111551484  FZD6; frizzled-6 [KO:K02376]
111522969  FZD10; frizzled-10 [KO:K02842]
111547022  FZD9; frizzled-9 [KO:K02842]
111552076  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
111522423  LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 5-like [KO:K03068]
111523166  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
111521282  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
111526841  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
111538755  FRAT1; proto-oncogene FRAT1 [KO:K03069]
111534487  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
111543871  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111524116  AXIN1; axin-1 [KO:K02157]
111542510  AXIN2; axin-2 isoform X1 [KO:K04385]
111542693  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
111534247  adenomatous polyposis coli protein 2 [KO:K02085]
111555526  CTNNB1; catenin beta-1 [KO:K02105]
111552628  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
111540407  CSNK1A1L; casein kinase I [KO:K08957] [EC:2.7.11.1]
111529175  TCF7; transcription factor 7 isoform X1 [KO:K02620]
111551134  TCF7L1; transcription factor 7-like 1 [KO:K04490]
111538904  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
111547880  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
111550563  MYC; myc proto-oncogene protein [KO:K04377]
111522272  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111528337  TERT; telomerase reverse transcriptase isoform X1 [KO:K11126] [EC:2.7.7.49]
111547933  EGF; pro-epidermal growth factor [KO:K04357]
111555709  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111537465  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
111543732  SHC1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
111528883  SHC2; SHC-transforming protein 2 [KO:K17447]
111527961  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
111552722  SHC4; SHC-transforming protein 4 [KO:K17449]
111542428  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
111545353  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
111549528  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
111540622  KRAS; GTPase KRas isoform X1 [KO:K07827]
111549619  NRAS; GTPase NRas [KO:K07828]
111536410  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
111521522  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
111546904  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111548354  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111521954  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111530673  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111525729  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
111521403  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111544647  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111523340  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111554247  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111539891  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111548774  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
111554120  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111545216  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111538340  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111526309  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
111522215  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X2 [KO:K04688] [EC:2.7.11.1]
111528437  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
111523141  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
111552085  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
111541872  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
111553938  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
111549709  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
111523077  RB1; retinoblastoma-associated protein [KO:K06618]
111548151  E2F1; transcription factor E2F1 [KO:K17454]
111547703  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
111541114  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
111554142  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
111537117  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
111555026  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
111536462  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
111526524  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
111539679  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
111548349  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
111539654  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
111537212  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
111541390  CDH1; cadherin-1 isoform X1 [KO:K05689]
111528554  CTNNA1; catenin alpha-1 isoform X1 [KO:K05691]
111551139  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
111537944  CTNNA3; catenin alpha-3 isoform X1 [KO:K05691]
111537394  JUP; junction plakoglobin [KO:K10056]
111552446  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
111553422  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
111523283  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
111546245  FGF2; fibroblast growth factor 2 [KO:K18497]
111528737  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
111534218  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
111552814  FGF7; fibroblast growth factor 7 [KO:K04358]
111522276  FGF3; fibroblast growth factor 3 [KO:K04358]
111522486  FGF4; fibroblast growth factor 4 [KO:K04358]
111535838  FGF6; fibroblast growth factor 6 [KO:K04358]
111536051  FGF16; fibroblast growth factor 16 [KO:K04358]
111525307  FGF9; fibroblast growth factor 9 [KO:K04358]
111547150  FGF18; fibroblast growth factor 18 [KO:K04358]
111547417  FGF20; fibroblast growth factor 20 [KO:K04358]
111538699  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
111549401  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
111522468  FGF19; fibroblast growth factor 19 [KO:K22603]
111519986  FGF21; fibroblast growth factor 21 [KO:K22429]
111535828  FGF23; fibroblast growth factor 23 [KO:K22428]
111550787  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
111551919  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
pteh04010  MAPK signaling pathway
pteh04110  Cell cycle
pteh04115  p53 signaling pathway
pteh04151  PI3K-Akt signaling pathway
pteh04310  Wnt signaling pathway
pteh04350  TGF-beta signaling pathway
pteh04520  Adherens junction
KO pathway
ko05226   
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