KEGG   PATHWAY: btax05226
Entry
btax05226                   Pathway                                
Name
Gastric cancer - Budorcas taxicolor (takin)
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
btax05226  Gastric cancer
btax05226

Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128057819  CDX2; homeobox protein CDX-2 [KO:K22234]
128068935  MUC2; mucin-2 [KO:K10955]
128059292  CDH17; cadherin-17 [KO:K06811]
128045710  REG4; regenerating islet-derived protein 4 [KO:K22244]
128046575  ABCB1; ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
128046961  SHH; sonic hedgehog protein [KO:K11988]
128049822  LOW QUALITY PROTEIN: cellular tumor antigen p53-like [KO:K04451]
128064672  TP53; cellular tumor antigen p53 [KO:K04451]
128056953  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
128050874  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
128044871  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
128052323  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
128064207  BAX; apoptosis regulator BAX [KO:K02159]
128056082  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
128059803  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
128053849  POLK; LOW QUALITY PROTEIN: DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
128068408  RARB; retinoic acid receptor beta [KO:K08528]
128056978  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
128055533  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
128044655  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
128048884  WNT1; proto-oncogene Wnt-1 [KO:K03209]
128044967  WNT2B; protein Wnt-2b [KO:K00182]
128046758  WNT2; protein Wnt-2 [KO:K00182]
128051398  WNT3A; protein Wnt-3a [KO:K00312]
128065491  WNT3; proto-oncogene Wnt-3 [KO:K00312]
128064929  WNT4; protein Wnt-4 [KO:K00408]
128051429  WNT5A; protein Wnt-5a [KO:K00444]
128047274  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
128043631  WNT6; protein Wnt-6 [KO:K00445]
128054243  WNT7A; protein Wnt-7a [KO:K00572]
128048826  WNT7B; protein Wnt-7b [KO:K00572]
128051617  WNT8A; protein Wnt-8a [KO:K00714]
128067661  WNT8B; protein Wnt-8b [KO:K00714]
128051174  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
128065456  WNT9B; protein Wnt-9b [KO:K01064]
128043684  WNT10A; protein Wnt-10a [KO:K01357]
128048628  WNT10B; protein Wnt-10b [KO:K01357]
128060249  WNT11; protein Wnt-11 isoform X1 [KO:K01384]
128046389  WNT16; protein Wnt-16 [KO:K01558]
128070496  FZD7; frizzled-7 [KO:K02432]
128046799  FZD1; frizzled-1 [KO:K02432]
128065200  FZD2; frizzled-2 [KO:K02235]
128052483  FZD3; frizzled-3 [KO:K02329]
128068654  FZD4; frizzled-4 [KO:K02354]
128071105  frizzled-5 [KO:K02375]
128058547  FZD8; frizzled-8 [KO:K02375]
128065941  FZD5; frizzled-5 [KO:K02375]
128059374  FZD6; frizzled-6 [KO:K02376]
128043337  FZD9; frizzled-9 [KO:K02842]
128062458  FZD10; frizzled-10 [KO:K02842]
128069156  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
128048011  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
128064845  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
128045751  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
128061181  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
128067878  FRAT1; proto-oncogene FRAT1 [KO:K03069]
128067855  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
128043889  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
128061865  AXIN1; axin-1 isoform X1 [KO:K02157]
128065073  AXIN2; axin-2 [KO:K04385]
128050459  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
128053813  APC; adenomatous polyposis coli protein [KO:K02085]
128058237  CTNNB1; catenin beta-1 [KO:K02105]
128050290  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
128069547  LOW QUALITY PROTEIN: casein kinase I-like [KO:K08957] [EC:2.7.11.1]
128070116  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
128070471  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
128070472  casein kinase I [KO:K08957] [EC:2.7.11.1]
128070473  casein kinase I [KO:K08957] [EC:2.7.11.1]
128070474  casein kinase I [KO:K08957] [EC:2.7.11.1]
128050871  TCF7; transcription factor 7 [KO:K02620]
128056483  TCF7L1; transcription factor 7-like 1 [KO:K04490]
128067999  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
128049642  LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
128059120  MYC; myc proto-oncogene protein [KO:K04377]
128069030  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
128066195  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
128050008  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
128051614  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
128064538  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
128044445  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
128051196  SHC2; SHC-transforming protein 2 [KO:K17447]
128052614  SHC3; SHC-transforming protein 3 [KO:K17448]
128054009  SHC4; SHC-transforming protein 4 [KO:K17449]
128064562  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
128053892  SOS2; son of sevenless homolog 2 [KO:K03099]
128055374  SOS1; son of sevenless homolog 1 [KO:K03099]
128068689  HRAS; GTPase HRas isoform X1 [KO:K02833]
128047937  KRAS; GTPase KRas [KO:K07827]
128044537  NRAS; GTPase NRas [KO:K07828]
128070468  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
128046969  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
128043403  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128054045  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128050664  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
128043958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128062160  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128045803  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
128061813  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128068699  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128050540  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
128044474  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
128066235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
128063870  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128067048  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061491  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061687  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
128064578  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
128068526  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
128067358  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
128060723  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
128047650  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
128047622  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
128063478  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
128059332  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
128057539  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
128058399  E2F1; transcription factor E2F1 [KO:K17454]
128043619  E2F2; transcription factor E2F2 [KO:K09389]
128056580  E2F3; transcription factor E2F3 [KO:K06620]
128063320  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
128061503  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
128053888  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
128051987  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
128048354  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
128067292  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
128054493  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
128067298  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
128052514  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
128063421  CDH1; cadherin-1 [KO:K05689]
128051249  CTNNA1; catenin alpha-1 [KO:K05691]
128047332  CTNNA3; catenin alpha-3 [KO:K05691]
128055255  CTNNA2; catenin alpha-2 [KO:K05691]
128064548  JUP; junction plakoglobin [KO:K10056]
128046678  HGF; hepatocyte growth factor [KO:K05460]
128046469  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
128050845  FGF1; fibroblast growth factor 1 [KO:K18496]
128062082  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
128049947  FGF5; fibroblast growth factor 5 [KO:K04358]
128069166  FGF4; fibroblast growth factor 4 [KO:K04358]
128069196  FGF3; fibroblast growth factor 3 [KO:K04358]
128070322  FGF16; fibroblast growth factor 16 [KO:K04358]
128057718  FGF9; fibroblast growth factor 9 [KO:K04358]
128051703  FGF22; fibroblast growth factor 22 [KO:K04358]
128052704  FGF17; fibroblast growth factor 17 [KO:K04358]
128065968  FGF10; fibroblast growth factor 10 [KO:K04358]
128066262  FGF18; fibroblast growth factor 18 [KO:K04358]
128053785  FGF7; fibroblast growth factor 7 [KO:K04358]
128048008  FGF6; fibroblast growth factor 6 [KO:K04358]
128067938  FGF8; fibroblast growth factor 8 [KO:K04358]
128068355  FGF20; fibroblast growth factor 20 [KO:K04358]
128069264  FGF19; fibroblast growth factor 19 [KO:K22603]
128064178  FGF21; fibroblast growth factor 21 [KO:K22429]
128048959  FGF23; fibroblast growth factor 23 [KO:K22428]
128067669  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
128062226  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
btax04010  MAPK signaling pathway
btax04110  Cell cycle
btax04115  p53 signaling pathway
btax04151  PI3K-Akt signaling pathway
btax04310  Wnt signaling pathway
btax04350  TGF-beta signaling pathway
btax04520  Adherens junction
KO pathway
ko05226   
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