KEGG   PATHWAY: mmyo05226
Entry
mmyo05226                   Pathway                                
Name
Gastric cancer - Myotis myotis (greater mouse-eared bat)
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
mmyo05226  Gastric cancer
mmyo05226

Organism
Myotis myotis (greater mouse-eared bat) [GN:mmyo]
Gene
118652105  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
118648947  MUC2; mucin-2 [KO:K10955]
118670962  CDH17; cadherin-17 [KO:K06811]
118672657  REG4; regenerating islet-derived protein 4 [KO:K22244]
118666260  ABCB1; ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
118679449  SHH; sonic hedgehog protein [KO:K11988]
118672084  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
118659964  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
118658909  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
118652529  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
118676452  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
118655437  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
118679638  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
118665064  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
118656304  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
118668241  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
118666894  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
118679517  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
118673063  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
118650977  WNT1; proto-oncogene Wnt-1 [KO:K03209]
118672911  WNT2B; protein Wnt-2b [KO:K00182]
118666478  WNT2; protein Wnt-2 [KO:K00182]
118658755  WNT3A; protein Wnt-3a isoform X1 [KO:K00312]
118672219  WNT3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
118676694  WNT4; protein Wnt-4 [KO:K00408]
118650248  WNT5B; protein Wnt-5b [KO:K00444]
118667971  WNT5A; protein Wnt-5a [KO:K00444]
118662211  WNT6; protein Wnt-6 [KO:K00445]
118650243  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
118677354  WNT7A; protein Wnt-7a [KO:K00572]
118658912  WNT8A; protein Wnt-8a [KO:K00714]
118669850  WNT8B; protein Wnt-8b [KO:K00714]
118658374  WNT9A; protein Wnt-9a [KO:K01064]
118671436  WNT9B; protein Wnt-9b [KO:K01064]
118651671  WNT10B; protein Wnt-10b [KO:K01357]
118661959  WNT10A; protein Wnt-10a isoform X1 [KO:K01357]
118664619  WNT11; protein Wnt-11 [KO:K01384]
118666468  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
118666245  FZD1; frizzled-1 [KO:K02432]
118661773  FZD7; frizzled-7 [KO:K02432]
118672294  FZD2; frizzled-2 [KO:K02235]
118658774  FZD3; frizzled-3 isoform X1 [KO:K02329]
118664546  FZD4; frizzled-4 [KO:K02354]
118661425  FZD5; frizzled-5 [KO:K02375]
118676314  FZD8; frizzled-8 [KO:K02375]
118670703  FZD6; frizzled-6 [KO:K02376]
118653033  FZD10; LOW QUALITY PROTEIN: frizzled-10 [KO:K02842]
118656623  FZD9; frizzled-9 [KO:K02842]
118649950  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
118665196  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
118677642  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
118655561  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
118672041  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
118669908  FRAT1; proto-oncogene FRAT1 [KO:K03069]
118669907  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
118675932  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
118652848  AXIN1; axin-1 isoform X1 [KO:K02157]
118654322  LOW QUALITY PROTEIN: axin-1-like [KO:K02157]
118671617  AXIN2; axin-2 isoform X1 [KO:K04385]
118658707  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
118655759  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
118668371  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
118657973  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
118665504  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118653594  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118654184  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118662055  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118657631  TCF7; transcription factor 7 isoform X1 [KO:K02620]
118668800  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
118669739  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
118673131  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
118670599  MYC; myc proto-oncogene protein [KO:K04377]
118665181  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
118656828  TERT; telomerase reverse transcriptase isoform X1 [KO:K11126] [EC:2.7.7.49]
118672981  EGF; pro-epidermal growth factor [KO:K04357]
118665909  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
118671218  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
118669819  LOW QUALITY PROTEIN: SHC-transforming protein 1-like [KO:K06279]
118672782  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
118659254  SHC2; SHC-transforming protein 2 [KO:K17447]
118652528  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
118651538  SHC4; SHC-transforming protein 4 [KO:K17449]
118671153  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
118669078  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
118654741  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
118648965  HRAS; GTPase HRas isoform X1 [KO:K02833]
118649554  KRAS; GTPase KRas isoform X1 [KO:K07827]
118672986  NRAS; GTPase NRas [KO:K07828]
118653778  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
118666337  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
118668076  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118654213  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
118657986  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
118678650  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
118656605  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
118677590  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118668125  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118675045  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118675217  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
118656203  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118657573  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
118678909  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118655031  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118674834  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118675322  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
118649569  LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
118649570  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
118671643  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
118665219  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
118663765  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
118668289  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
118650327  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
118651193  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
118653038  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
118670629  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
118651068  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
118663841  E2F1; transcription factor E2F1 [KO:K17454]
118676426  E2F2; transcription factor E2F2 [KO:K09389]
118676306  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
118674276  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
118678846  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
118658350  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
118667263  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
118668257  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
118662725  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
118654312  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
118662909  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
118667590  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
118674502  CDH1; cadherin-1 isoform X1 [KO:K05689]
118658375  CTNNA1; catenin alpha-1 isoform X1 [KO:K05691]
118668808  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
118670057  CTNNA3; catenin alpha-3 [KO:K05691]
118671536  junction plakoglobin [KO:K10056]
118666274  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
118666481  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
118658742  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
118657980  FGF2; fibroblast growth factor 2 [KO:K18497]
118651638  FGF7; fibroblast growth factor 7 [KO:K04358]
118649770  FGF6; fibroblast growth factor 6 [KO:K04358]
118651170  FGF20; fibroblast growth factor 20 [KO:K04358]
118657925  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
118657946  FGF18; fibroblast growth factor 18 isoform X1 [KO:K04358]
118658335  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
118651945  FGF9; fibroblast growth factor 9 isoform X1 [KO:K04358]
118653962  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
118654722  FGF16; fibroblast growth factor 16 [KO:K04358]
118670266  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
118664022  FGF3; fibroblast growth factor 3 [KO:K04358]
118664023  FGF4; fibroblast growth factor 4 [KO:K04358]
118656661  FGF10; fibroblast growth factor 10 [KO:K04358]
118664060  FGF19; fibroblast growth factor 19 [KO:K22603]
118655446  FGF21; fibroblast growth factor 21 [KO:K22429]
118651326  FGF23; fibroblast growth factor 23 [KO:K22428]
118655613  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
118659207  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
mmyo04010  MAPK signaling pathway
mmyo04110  Cell cycle
mmyo04115  p53 signaling pathway
mmyo04151  PI3K-Akt signaling pathway
mmyo04310  Wnt signaling pathway
mmyo04350  TGF-beta signaling pathway
mmyo04520  Adherens junction
KO pathway
ko05226   
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