KEGG   PATHWAY: mcc05226
Entry
mcc05226                    Pathway                                
Name
Gastric cancer - Macaca mulatta (rhesus monkey)
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
mcc05226  Gastric cancer
mcc05226

Disease
H00018  Gastric cancer
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
100423838  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100424087  AXIN1; axin-1 isoform X1 [KO:K02157]
100429884  TERC; telomerase RNA component [KO:K22183]
106992315  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
106992736  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
114672263  [KO:K10140]
114675335  [KO:K04388] [EC:2.7.11.30]
114675385  [KO:K11126] [EC:2.7.7.49]
114675515  [KO:K14021]
574136  FGF2; fibroblast growth factor 2 [KO:K18497]
574235  ABCB1; multidrug resistance protein 1 [KO:K05658] [EC:7.6.2.2]
574265  CTNNB1; catenin beta-1 [KO:K02105]
574275  SHC3; SHC-transforming protein 3 [KO:K17448]
574320  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
574345  FGF7; fibroblast growth factor 7 precursor [KO:K04358]
574385  CTNNA1; catenin alpha-1 [KO:K05691]
613027  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
693419  WNT7A; protein Wnt-7a [KO:K00572]
693443  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
693554  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
694069  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
694560  TCF7L1; transcription factor 7-like 1 isoform X2 [KO:K04490]
694625  FZD6; frizzled-6 precursor [KO:K02376]
694626  MYC; myc proto-oncogene protein [KO:K04377]
694725  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
694807  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
695190  CSNK1A1L; casein kinase I isoform alpha-like [KO:K08957] [EC:2.7.11.1]
695776  LEF1; lymphoid enhancer-binding factor 1 isoform X3 [KO:K04492]
695843  LRP6; low-density lipoprotein receptor-related protein 6 precursor [KO:K03068]
695896  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
695966  REG4; regenerating islet-derived protein 4 [KO:K22244]
696040  CTNNA3; catenin alpha-3 [KO:K05691]
696200  WNT3A; protein Wnt-3a [KO:K00312]
696326  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
696845  WNT11; protein Wnt-11 isoform X2 [KO:K01384]
697188  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
697573  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
697581  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
697747  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
697835  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
698619  EGF; pro-epidermal growth factor isoform X2 [KO:K04357]
698782  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
698830  HRAS; GTPase HRas [KO:K02833]
698886  CDH17; cadherin-17 isoform X1 [KO:K06811]
698996  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
700367  GAB1; GRB2-associated-binding protein 1 [KO:K09593]
700382  CCNE2; G1/S-specific cyclin-E2 isoform X2 [KO:K06626]
700485  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
700573  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
700589  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
700591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
700692  WNT10A; protein Wnt-10a [KO:K01357]
701054  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
701584  FGF10; fibroblast growth factor 10 precursor [KO:K04358]
701759  TCF7L2; transcription factor 7-like 2 isoform X9 [KO:K04491]
701803  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
701847  FGF20; fibroblast growth factor 20 [KO:K04358]
702041  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
702072  FGF18; fibroblast growth factor 18 [KO:K04358]
702727  FGF22; fibroblast growth factor 22 precursor [KO:K04358]
703064  FZD7; frizzled-7 [KO:K02432]
703088  TGFBR2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
703239  TGFB3; transforming growth factor beta-3 precursor [KO:K13377]
703942  FZD1; frizzled-1 [KO:K02432]
704387  CDH1; cadherin-1 [KO:K05689]
704562  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
704754  FZD4; frizzled-4 precursor [KO:K02354]
704871  RB1; retinoblastoma-associated protein [KO:K06618]
704991  WNT2; protein Wnt-2 precursor [KO:K00182]
705601  SOS2; son of sevenless homolog 2 [KO:K03099]
705609  FRAT1; proto-oncogene FRAT1 [KO:K03069]
705612  FGF16; fibroblast growth factor 16 [KO:K04358]
705692  WNT5A; protein Wnt-5a isoform X2 [KO:K00444]
705713  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
705730  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
705773  WNT2B; protein Wnt-2b [KO:K00182]
705864  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
705970  FGF1; fibroblast growth factor 1 [KO:K18496]
706534  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
706659  FGF17; fibroblast growth factor 17 precursor [KO:K04358]
707169  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
707310  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
707345  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
707407  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
707540  TGFB2; transforming growth factor beta-2 precursor [KO:K13376]
707769  JUP; junction plakoglobin [KO:K10056]
707864  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
707977  KRAS; GTPase KRas [KO:K07827]
708316  HGF; hepatocyte growth factor isoform X3 [KO:K05460]
708368  FZD8; frizzled-8 [KO:K02375]
708906  WNT10B; protein Wnt-10b precursor [KO:K01357]
708918  FGF3; fibroblast growth factor 3 precursor [KO:K04358]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
709009  WNT1; proto-oncogene Wnt-1 [KO:K03209]
709016  FGF4; fibroblast growth factor 4 [KO:K04358]
709089  NRAS; GTPase NRas [KO:K07828]
709109  FGF19; fibroblast growth factor 19 [KO:K22603]
709209  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
709865  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
709959  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
710200  E2F2; transcription factor E2F2 [KO:K09389]
710234  TCF7; transcription factor 7 isoform X3 [KO:K02620]
710242  WNT8B; protein Wnt-8b [KO:K00714]
710415  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
710552  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
710643  FGF23; fibroblast growth factor 23 precursor [KO:K22428]
710739  FGF6; fibroblast growth factor 6 [KO:K04358]
710775  CSNK1A1; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
710796  FZD5; frizzled-5 [KO:K02375]
711002  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
711094  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
711257  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
711355  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
711979  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
712135  CTNNA2; catenin alpha-2 [KO:K05691]
712381  FZD2; frizzled-2 [KO:K02235]
713114  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
713764  WNT8A; protein Wnt-8a [KO:K00714]
713777  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
713813  DDB2; DNA damage-binding protein 2 [KO:K10140]
713839  FZD3; frizzled-3 precursor [KO:K02329]
713864  WNT7B; protein Wnt-7b isoform X2 [KO:K00572]
713904  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
714126  E2F1; transcription factor E2F1 [KO:K17454]
714381  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
714611  SHC4; SHC-transforming protein 4 [KO:K17449]
714717  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
714952  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
715949  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
716098  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
716170  TP53; cellular tumor antigen p53 [KO:K04451]
716392  FZD9; frizzled-9 [KO:K02842]
716553  SHH; sonic hedgehog protein [KO:K11988]
716877  WNT9B; protein Wnt-9b [KO:K01064]
716909  WNT3; proto-oncogene Wnt-3 [KO:K00312]
717368  RXRB; retinoic acid receptor RXR-beta isoform X2 [KO:K08525]
717812  FZD10; frizzled-10 [KO:K02842]
718288  FGF21; fibroblast growth factor 21 [KO:K22429]
718566  AXIN2; axin-2 isoform X1 [KO:K04385]
718948  BAX; apoptosis regulator BAX [KO:K02159]
718982  SHC1; SHC-transforming protein 1 [KO:K06279]
719199  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
719367  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
720903  MUC2; mucin-2 [KO:K10955]
721021  SHC2; SHC-transforming protein 2 [KO:K17447]
721324  FGF9; fibroblast growth factor 9 [KO:K04358]
721605  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
721685  WNT5B; protein Wnt-5b [KO:K00444]
721731  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X2 [KO:K04688] [EC:2.7.11.1]
721821  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
722068  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
722394  FGF8; fibroblast growth factor 8 [KO:K04358]
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
mcc04010  MAPK signaling pathway
mcc04110  Cell cycle
mcc04115  p53 signaling pathway
mcc04151  PI3K-Akt signaling pathway
mcc04310  Wnt signaling pathway
mcc04350  TGF-beta signaling pathway
mcc04520  Adherens junction
KO pathway
ko05226   

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