KEGG   PATHWAY: bta05226
Entry
bta05226                    Pathway                                
Name
Gastric cancer - Bos taurus (cow)
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
bta05226  Gastric cancer
bta05226

Disease
H00018  Gastric cancer
Organism
Bos taurus (cow) [GN:bta]
Gene
100137872  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100138040  SOS2; son of sevenless homolog 2 [KO:K03099]
100138998  [KO:K08957] [EC:2.7.11.1]
100139219  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100296627  [KO:K05658] [EC:7.6.2.2]
100298939  HRAS; GTPase HRas isoform 1 [KO:K02833]
100300257  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
100337066  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
100847184  [KO:K02833]
101905399  [KO:K04368] [EC:2.7.12.2]
280730  BAX; apoptosis regulator BAX [KO:K02159]
280855  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
280991  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
281020  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
281160  FGF1; fibroblast growth factor 1 [KO:K18496]
281161  FGF2; fibroblast growth factor 2 precursor [KO:K18497]
281542  TP53; cellular tumor antigen p53 [KO:K04451]
281585  ABCB1; LOW QUALITY PROTEIN: ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
282089  TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
282306  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
282307  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
282308  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
282382  TGFBR1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
282637  CDH1; cadherin-1 precursor [KO:K05689]
282684  CSNK1A1; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
282879  HGF; hepatocyte growth factor precursor [KO:K05460]
286821  SHH; sonic hedgehog protein [KO:K11988]
286865  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
326284  FGF8; fibroblast growth factor 8 precursor [KO:K04358]
326285  FGF10; fibroblast growth factor 10 precursor [KO:K04358]
327672  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
379035  TERC; telomerase RNA component [KO:K22183]
404181  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
404193  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
407217  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
445416  FZD4; frizzled-4 precursor [KO:K02354]
445417  FZD1; frizzled-1 [KO:K02432]
445418  FZD6; frizzled-6 [KO:K02376]
445419  FZD3; frizzled-3 precursor [KO:K02329]
445420  WNT2B; protein Wnt-2b [KO:K00182]
445543  JUP; junction plakoglobin [KO:K10056]
493729  WNT2; protein Wnt-2 precursor [KO:K00182]
504357  AXIN1; axin-1 [KO:K02157]
504531  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
504939  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
504943  RXRB; retinoic acid receptor RXR-beta [KO:K08525]
505075  WNT6; protein Wnt-6 precursor [KO:K00445]
505463  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
505664  FRAT1; proto-oncogene FRAT1 [KO:K03069]
505709  ERBB2; receptor tyrosine-protein kinase erbB-2 precursor [KO:K05083] [EC:2.7.10.1]
506083  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
506322  NRAS; GTPase NRas [KO:K07828]
507196  SHC1; SHC-transforming protein 1 isoform b [KO:K06279]
507526  CDH17; cadherin-17 precursor [KO:K06811]
507554  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
508008  WNT5B; protein Wnt-5b precursor [KO:K00444]
509500  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
510434  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
511077  MYC; myc proto-oncogene protein [KO:K04377]
511308  WNT9A; protein Wnt-9a [KO:K01064]
511619  AXIN2; axin-2 [KO:K04385]
512613  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
512696  SHC3; SHC-transforming protein 3 isoform X3 [KO:K17448]
513497  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
514090  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
515125  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
515303  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
515323  FZD10; frizzled-10 precursor [KO:K02842]
516010  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
517948  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
518884  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
519217  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
519357  DDB2; DNA damage-binding protein 2 [KO:K10140]
519657  FGF22; fibroblast growth factor 22 precursor [KO:K04358]
521196  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
521364  FZD9; LOW QUALITY PROTEIN: frizzled-9 [KO:K02842]
521475  FGF19; fibroblast growth factor 19 [KO:K22603]
522467  WNT3A; protein Wnt-3a [KO:K00312]
523325  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
524255  FZD7; frizzled-7 precursor [KO:K02432]
524530  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
524734  SHC4; SHC-transforming protein 4 [KO:K17449]
526572  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
526848  CTNNA1; catenin alpha-1 [KO:K05691]
527124  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
527492  CTNNA2; catenin alpha-2 [KO:K05691]
530005  WNT5A; protein Wnt-5a [KO:K00444]
530239  FGF23; fibroblast growth factor 23 [KO:K22428]
530315  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
531391  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
533199  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
533233  APC; adenomatous polyposis coli protein [KO:K02085]
533455  SHC2; SHC-transforming protein 2 [KO:K17447]
533526  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
533652  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
533782  WNT7A; protein Wnt-7a [KO:K00572]
533929  FGF18; fibroblast growth factor 18 precursor [KO:K04358]
534069  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
534450  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
534712  RB1; retinoblastoma-associated protein [KO:K06618]
534923  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
535298  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
535369  E2F1; transcription factor E2F1 [KO:K17454]
535376  TGFBR2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
535399  LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
536051  BRAF; serine/threonine-protein kinase B-raf isoform X9 [KO:K04365] [EC:2.7.11.1]
536328  LRP6; low-density lipoprotein receptor-related protein 6 isoform X2 [KO:K03068]
536771  FGF5; fibroblast growth factor 5 precursor [KO:K04358]
537330  WNT10A; protein Wnt-10a precursor [KO:K01357]
537682  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
538436  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
538507  FZD2; frizzled-2 [KO:K02235]
538536  FZD5; frizzled-5 [KO:K02375]
538627  WNT16; protein Wnt-16 precursor [KO:K01558]
538720  WNT8B; protein Wnt-8b [KO:K00714]
538957  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
539003  CTNNB1; catenin beta-1 [KO:K02105]
539083  FGF20; fibroblast growth factor 20 [KO:K04358]
539144  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
539203  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X2 [KO:K02353]
539337  WNT10B; protein Wnt-10b [KO:K01357]
540085  GAB1; GRB2-associated-binding protein 1 [KO:K09593]
540199  WNT8A; protein Wnt-8a [KO:K00714]
540248  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
540317  FGF6; fibroblast growth factor 6 [KO:K04358]
540421  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
540481  TCF7L2; transcription factor 7-like 2 [KO:K04491]
540662  WNT1; proto-oncogene Wnt-1 precursor [KO:K03209]
540753  WNT3; proto-oncogene Wnt-3 precursor [KO:K00312]
540758  FGF16; fibroblast growth factor 16 [KO:K04358]
541140  KRAS; GTPase KRas [KO:K07827]
541184  E2F3; transcription factor E2F3 [KO:K06620]
541218  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
541243  WNT9B; protein Wnt-9b [KO:K01064]
613288  WNT11; protein Wnt-11 [KO:K01384]
613515  [KO:K08957] [EC:2.7.11.1]
613731  FGF9; fibroblast growth factor 9 [KO:K04358]
614312  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
616885  FGF7; fibroblast growth factor 7 precursor [KO:K04358]
616895  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
616913  FZD8; frizzled-8 [KO:K02375]
617024  E2F2; transcription factor E2F2 isoform X2 [KO:K09389]
618405  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
618474  FGF4; fibroblast growth factor 4 precursor [KO:K04358]
618481  FGF3; fibroblast growth factor 3 [KO:K04358]
618679  CDX2; homeobox protein CDX-2 [KO:K22234]
767907  REG4; regenerating islet-derived protein 4 precursor [KO:K22244]
780777  CTNNA3; catenin alpha-3 [KO:K05691]
782690  TCF7; transcription factor 7 [KO:K02620]
785423  CSNK1B; casein kinase I isoform beta [KO:K08957] [EC:2.7.11.1]
785576  FGF21; fibroblast growth factor 21 [KO:K22429]
789571  MUC2; LOW QUALITY PROTEIN: mucin-2 [KO:K10955]
789600  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
790875  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
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
bta04010  MAPK signaling pathway
bta04110  Cell cycle
bta04115  p53 signaling pathway
bta04151  PI3K-Akt signaling pathway
bta04310  Wnt signaling pathway
bta04350  TGF-beta signaling pathway
bta04520  Adherens junction
KO pathway
ko05226   

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