KEGG   PATHWAY: mmur05226
Entry
mmur05226                   Pathway                                
Name
Gastric cancer - Microcebus murinus (gray mouse lemur)
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
mmur05226  Gastric cancer
mmur05226

Disease
H00018  Gastric cancer
Organism
Microcebus murinus (gray mouse lemur) [GN:mmur]
Gene
105855026  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105855775  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
105855821  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105855966  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
105856263  AXIN1; axin-1 isoform X1 [KO:K02157]
105856944  FZD7; frizzled-7 [KO:K02432]
105857128  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
105857286  KRAS; GTPase KRas isoform X1 [KO:K07827]
105857652  WNT10A; protein Wnt-10a [KO:K01357]
105857713  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
105857795  FGF10; fibroblast growth factor 10 [KO:K04358]
105857966  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
105858435  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
105858813  FZD9; frizzled-9 [KO:K02842]
105858901  CDX2; homeobox protein CDX-2 [KO:K22234]
105858954  CDH1; LOW QUALITY PROTEIN: cadherin-1 [KO:K05689]
105858956  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
105859122  CTNNA2; catenin alpha-2 isoform X2 [KO:K05691]
105859125  [KO:K05691]
105860401  WNT11; protein Wnt-11 [KO:K01384]
105860427  FZD4; frizzled-4 [KO:K02354]
105860510  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
105860538  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
105860555  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
105860762  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
105860825  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
105860843  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
105861093  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105861439  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105861442  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105861590  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
105861654  AXIN2; axin-2 isoform X1 [KO:K04385]
105862086  CSNK1A1L; casein kinase I [KO:K08957] [EC:2.7.11.1]
105862190  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
105862501  FGF1; fibroblast growth factor 1 [KO:K18496]
105862517  CTNNA1; catenin alpha-1 isoform X1 [KO:K05691]
105862521  WNT8A; protein Wnt-8a isoform X3 [KO:K00714]
105862660  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105863547  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105863673  WNT3; proto-oncogene Wnt-3 [KO:K00312]
105863738  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105864316  FZD5; frizzled-5 [KO:K02375]
105864522  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
105864858  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
105864946  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105865198  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
105865199  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105865602  BAX; apoptosis regulator BAX isoform X2 [KO:K02159]
105865679  FGF21; fibroblast growth factor 21 [KO:K22429]
105866012  E2F1; transcription factor E2F1 [KO:K17454]
105866146  FGF16; fibroblast growth factor 16 [KO:K04358]
105867172  FGF18; fibroblast growth factor 18 [KO:K04358]
105867344  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
105867353  WNT16; protein Wnt-16 [KO:K01558]
105867396  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
105867398  FGF19; fibroblast growth factor 19 [KO:K22603]
105867400  FGF3; fibroblast growth factor 3 [KO:K04358]
105867413  FGF4; fibroblast growth factor 4 [KO:K04358]
105867475  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
105867511  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
105867678  SOS2; son of sevenless homolog 2 [KO:K03099]
105868083  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105868496  WNT10B; protein Wnt-10b [KO:K01357]
105868760  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105869115  TGFB1; transforming growth factor beta-1 isoform X1 [KO:K13375]
105869202  WNT1; proto-oncogene Wnt-1 [KO:K03209]
105869368  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
105869373  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
105869792  REG4; regenerating islet-derived protein 4 [KO:K22244]
105869975  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
105870237  CTNNA3; catenin alpha-3 isoform X1 [KO:K05691]
105870697  [KO:K04371] [EC:2.7.11.24]
105870727  FGF7; fibroblast growth factor 7 [KO:K04358]
105870730  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
105870804  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
105870856  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
105871124  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105871982  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
105872026  JUP; junction plakoglobin [KO:K10056]
105872099  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
105872305  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
105872329  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
105872762  FZD10; frizzled-10 [KO:K02842]
105872856  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105873000  FRAT1; proto-oncogene FRAT1 [KO:K03069]
105873009  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
105873192  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
105873244  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
105873607  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
105873639  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
105873781  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
105873938  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105873977  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
105873984  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105874032  HRAS; GTPase HRas [KO:K02833]
105874091  MUC2; LOW QUALITY PROTEIN: mucin-2 [KO:K10955]
105874193  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
105874233  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
105874413  CTNNB1; catenin beta-1 [KO:K02105]
105874527  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
105875160  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
105875662  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105875671  CDH17; cadherin-17 [KO:K06811]
105876163  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
105876174  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105876452  TERT; telomerase reverse transcriptase isoform X1 [KO:K11126] [EC:2.7.7.49]
105876584  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
105876702  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105876728  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
105876768  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105877006  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
105877164  FZD3; LOW QUALITY PROTEIN: frizzled-3 [KO:K02329]
105877217  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
105877483  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105877486  TP53; cellular tumor antigen p53 [KO:K04451]
105877644  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
105877796  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105877972  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
105878710  NRAS; GTPase NRas [KO:K07828]
105878754  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
105878831  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
105878875  FGF9; fibroblast growth factor 9 [KO:K04358]
105878936  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105879346  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
105879365  ABCB1; multidrug resistance protein 1 [KO:K05658] [EC:7.6.2.2]
105879391  FZD1; frizzled-1 [KO:K02432]
105879917  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105880812  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
105881062  [KO:K01064]
105881219  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105881454  FGF6; fibroblast growth factor 6 [KO:K04358]
105881457  FGF23; fibroblast growth factor 23 [KO:K22428]
105881857  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105881860  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
105882072  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
105882153  FZD6; frizzled-6 isoform X1 [KO:K02376]
105882525  FGF20; fibroblast growth factor 20 [KO:K04358]
105882676  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105882748  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
105883183  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
105883225  SHH; sonic hedgehog protein [KO:K11988]
105883482  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
105883515  WNT9B; protein Wnt-9b [KO:K01064]
105883521  FZD2; frizzled-2 [KO:K02235]
105884529  SOS1; son of sevenless homolog 1 [KO:K03099]
105884857  DDB2; DNA damage-binding protein 2 [KO:K10140]
105884926  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
105885999  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
105886039  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
105886063  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109730641  LRP5L; LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 5-like protein [KO:K03068]
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
mmur04010  MAPK signaling pathway
mmur04110  Cell cycle
mmur04115  p53 signaling pathway
mmur04151  PI3K-Akt signaling pathway
mmur04310  Wnt signaling pathway
mmur04350  TGF-beta signaling pathway
mmur04520  Adherens junction
KO pathway
ko05226   

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