KEGG   PATHWAY: ppam05226
Entry
ppam05226                   Pathway                                
Name
Gastric cancer - Pteronotus mesoamericanus (Parnell's mustached 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
ppam05226  Gastric cancer
ppam05226

Organism
Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]
Gene
129073412  CDX2; homeobox protein CDX-2 [KO:K22234]
129068443  MUC2; LOW QUALITY PROTEIN: mucin-2 [KO:K10955]
129084136  CDH17; cadherin-17 [KO:K06811]
129063708  REG4; regenerating islet-derived protein 4 [KO:K22244]
129063076  ABCB1; ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
129071477  SHH; sonic hedgehog protein isoform X1 [KO:K11988]
129072290  TP53; cellular tumor antigen p53 [KO:K04451]
129067419  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
129082291  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
129069921  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
129081112  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
129082924  BAX; apoptosis regulator BAX [KO:K02159]
129066993  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
129081434  DDB2; DNA damage-binding protein 2 [KO:K10140]
129074622  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
129087946  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
129079171  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
129067366  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
129082073  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
129084670  WNT1; proto-oncogene Wnt-1 [KO:K03209]
129063195  WNT2; protein Wnt-2 [KO:K00182]
129063930  WNT2B; protein Wnt-2b [KO:K00182]
129071521  WNT3; proto-oncogene Wnt-3 [KO:K00312]
129079093  WNT3A; protein Wnt-3a [KO:K00312]
129068971  WNT4; protein Wnt-4 [KO:K00408]
129088518  WNT5A; protein Wnt-5a [KO:K00444]
129073424  WNT5B; protein Wnt-5b [KO:K00444]
129080635  WNT6; protein Wnt-6 [KO:K00445]
129077914  WNT7B; protein Wnt-7b [KO:K00572]
129071686  WNT7A; protein Wnt-7a [KO:K00572]
129077118  WNT8B; protein Wnt-8b [KO:K00714]
129066317  WNT8A; protein Wnt-8a [KO:K00714]
129071596  WNT9B; protein Wnt-9b [KO:K01064]
129079070  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
129084671  WNT10B; protein Wnt-10b [KO:K01357]
129080634  WNT10A; protein Wnt-10a [KO:K01357]
129072640  WNT11; protein Wnt-11 [KO:K01384]
129062854  WNT16; protein Wnt-16 [KO:K01558]
129063044  FZD1; frizzled-1 [KO:K02432]
129080422  FZD7; frizzled-7 [KO:K02432]
129086682  FZD2; frizzled-2 [KO:K02235]
129072540  FZD3; frizzled-3 [KO:K02329]
129072819  FZD4; frizzled-4 [KO:K02354]
129086008  FZD8; frizzled-8 [KO:K02375]
129080389  FZD5; frizzled-5 [KO:K02375]
129084260  FZD6; frizzled-6 isoform X1 [KO:K02376]
129083423  FZD9; frizzled-9 [KO:K02842]
129087122  FZD10; frizzled-10 [KO:K02842]
129068530  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
129085017  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
129077014  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
129072308  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
129079202  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
129077272  FRAT1; proto-oncogene FRAT1 [KO:K03069]
129077273  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
129069640  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129081256  AXIN1; axin-1 isoform X1 [KO:K02157]
129070231  AXIN2; axin-2 isoform X1 [KO:K04385]
129081677  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
129083908  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
129088214  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
129066556  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
129073328  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
129066685  TCF7; transcription factor 7 isoform X1 [KO:K02620]
129073949  TCF7L1; transcription factor 7-like 1 [KO:K04490]
129077183  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
129085299  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
129084081  MYC; myc proto-oncogene protein [KO:K04377]
129068523  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
129074407  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
129085287  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
129068919  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
129087036  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
129062405  SHC1; SHC-transforming protein 1 [KO:K06279]
129072430  SHC2; SHC-transforming protein 2 [KO:K17447]
129082357  SHC3; SHC-transforming protein 3 [KO:K17448]
129064266  SHC4; SHC-transforming protein 4 [KO:K17449]
129086587  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
129064134  son of sevenless homolog 2 isoform X1 [KO:K03099]
129066034  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
129073113  HRAS; GTPase HRas isoform X1 [KO:K02833]
129084969  KRAS; GTPase KRas isoform X1 [KO:K07827]
129063946  NRAS; GTPase NRas [KO:K07828]
129065223  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
129062984  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
129088423  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129064157  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129078155  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129078069  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129086248  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129075675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129076577  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129088291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129074969  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129069407  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129074590  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129076641  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129066231  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129073033  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129075656  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
129068535  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
129071563  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
129078764  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129087856  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
129085013  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
129084214  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
129068119  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
129080865  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
129070474  E2F1; transcription factor E2F1 [KO:K17454]
129068981  E2F2; transcription factor E2F2 [KO:K09389]
129085787  E2F3; transcription factor E2F3 [KO:K06620]
129076675  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
129072973  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
129065729  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
129079398  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
129088202  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
129078704  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
129064154  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
129078725  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
129082183  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
129075248  CDH1; cadherin-1 [KO:K05689]
129069949  CTNNA3; catenin alpha-3 [KO:K05691]
129066646  CTNNA1; catenin alpha-1 [KO:K05691]
129073940  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
129086957  JUP; junction plakoglobin [KO:K10056]
129063396  HGF; hepatocyte growth factor [KO:K05460]
129063382  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
129066585  FGF1; fibroblast growth factor 1 [KO:K18496]
129061435  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
129068332  FGF4; fibroblast growth factor 4 [KO:K04358]
129068458  FGF3; fibroblast growth factor 3 [KO:K04358]
129074873  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
129082327  FGF9; fibroblast growth factor 9 [KO:K04358]
129077291  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
129064258  FGF7; fibroblast growth factor 7 [KO:K04358]
129084108  FGF5; fibroblast growth factor 5 [KO:K04358]
129064694  FGF20; fibroblast growth factor 20 [KO:K04358]
129065350  FGF16; fibroblast growth factor 16 [KO:K04358]
129071959  FGF10; fibroblast growth factor 10 [KO:K04358]
129072488  FGF22; LOW QUALITY PROTEIN: fibroblast growth factor 22 [KO:K04358]
129066345  FGF18; fibroblast growth factor 18 [KO:K04358]
129074224  FGF6; fibroblast growth factor 6 [KO:K04358]
129068333  FGF19; fibroblast growth factor 19 [KO:K22603]
129082796  FGF21; fibroblast growth factor 21 [KO:K22429]
129074223  FGF23; fibroblast growth factor 23 [KO:K22428]
129077222  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
129062066  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
ppam04010  MAPK signaling pathway
ppam04110  Cell cycle
ppam04115  p53 signaling pathway
ppam04151  PI3K-Akt signaling pathway
ppam04310  Wnt signaling pathway
ppam04350  TGF-beta signaling pathway
ppam04520  Adherens junction
KO pathway
ko05226   
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