KEGG   PATHWAY: pdic05226
Entry
pdic05226                   Pathway                                
Name
Gastric cancer - Phyllostomus discolor (pale spear-nosed 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
pdic05226  Gastric cancer
pdic05226

Organism
Phyllostomus discolor (pale spear-nosed bat) [GN:pdic]
Gene
114491128  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
114499192  MUC2; mucin-2 [KO:K10955]
114514689  CDH17; cadherin-17 [KO:K06811]
114489257  REG4; regenerating islet-derived protein 4 [KO:K22244]
114508093  ABCB1; ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
114507829  SHH; sonic hedgehog protein [KO:K11988]
114515376  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
114494317  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
114497596  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
114504094  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
114512579  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
114510992  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
114494928  BAK1; LOW QUALITY PROTEIN: bcl-2 homologous antagonist/killer [KO:K14021]
114499000  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
114505934  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
114501296  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
114507768  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
114495619  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
114511852  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
114512643  WNT1; proto-oncogene Wnt-1 [KO:K03209]
114488825  WNT2B; protein Wnt-2b [KO:K00182]
114508226  WNT2; protein Wnt-2 [KO:K00182]
114502706  WNT3; proto-oncogene Wnt-3 [KO:K00312]
114515231  WNT3A; protein Wnt-3a [KO:K00312]
114496757  WNT4; protein Wnt-4 [KO:K00408]
114513012  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
114501285  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
114494424  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
114490486  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
114513331  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
114510401  WNT8A; protein Wnt-8a [KO:K00714]
114498019  WNT8B; protein Wnt-8b [KO:K00714]
114503816  WNT9B; protein Wnt-9b [KO:K01064]
114515244  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
114514165  WNT10B; protein Wnt-10b [KO:K01357]
114495160  WNT10A; LOW QUALITY PROTEIN: protein Wnt-10a [KO:K01357]
114499625  WNT11; protein Wnt-11 [KO:K01384]
114507813  WNT16; protein Wnt-16 [KO:K01558]
114507693  FZD1; frizzled-1 [KO:K02432]
114494227  FZD7; frizzled-7 [KO:K02432]
114503439  FZD2; frizzled-2 [KO:K02235]
114503070  FZD3; frizzled-3 isoform X1 [KO:K02329]
114499235  FZD4; frizzled-4 [KO:K02354]
114492780  FZD8; frizzled-8 [KO:K02375]
114495243  FZD5; frizzled-5 [KO:K02375]
114514729  FZD6; frizzled-6 [KO:K02376]
114489789  FZD10; frizzled-10 [KO:K02842]
114512526  FZD9; frizzled-9 [KO:K02842]
114498631  LRP5; LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 5 [KO:K03068]
114513733  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
114490455  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X3 [KO:K02353]
114497866  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
114514992  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X3 [KO:K02353]
114495951  FRAT1; proto-oncogene FRAT1 [KO:K03069]
114497273  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
114490568  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
114496332  AXIN1; axin-1 isoform X2 [KO:K02157]
114502601  AXIN2; axin-2 [KO:K04385]
114502890  APC2; adenomatous polyposis coli protein 2 isoform X3 [KO:K02085]
114493533  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
114502148  CTNNB1; catenin beta-1 [KO:K02105]
114509574  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
114505513  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
114509934  TCF7; transcription factor 7 isoform X1 [KO:K02620]
114499663  TCF7L1; transcription factor 7-like 1 [KO:K04490]
114496676  TCF7L2; transcription factor 7-like 2 isoform X12 [KO:K04491]
114492280  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
114514698  MYC; myc proto-oncogene protein [KO:K04377]
114500683  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
114497449  TERT; telomerase reverse transcriptase isoform X1 [KO:K11126] [EC:2.7.7.49]
114492590  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
114507607  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
114502459  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
114488773  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
114504166  SHC2; SHC-transforming protein 2 [KO:K17447]
114512532  SHC3; SHC-transforming protein 3 [KO:K17448]
114492960  SHC4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449]
114503433  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
114499241  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
114493440  SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
114499504  HRAS; GTPase HRas isoform X2 [KO:K02833]
114512682  KRAS; GTPase KRas isoform X1 [KO:K07827]
114489186  NRAS; GTPase NRas [KO:K07828]
114504860  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
114507230  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
114501905  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
114491735  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
114503388  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114510156  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114496946  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114497407  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114490993  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114501452  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114496100  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
114502559  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
114501063  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114510957  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114512350  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114492688  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114496034  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
114502684  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
114499422  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
114507071  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
114501589  MLH1; DNA mismatch repair protein Mlh1 isoform X2 [KO:K08734]
114512889  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
114513129  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
114490138  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
114514877  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
114508470  RB1; LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]
114506109  E2F1; transcription factor E2F1 [KO:K17454]
114496714  E2F2; transcription factor E2F2 [KO:K09389]
114496340  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
114510965  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
114512425  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
114492736  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
114499676  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
114501577  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
114506330  SMAD2; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 2 [KO:K04500]
114491384  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
114506309  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
114506849  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
114488249  CDH1; cadherin-1 [KO:K05689]
114497515  CTNNA3; catenin alpha-3 isoform X1 [KO:K05691]
114499259  CTNNA2; catenin alpha-2 isoform X3 [KO:K05691]
114509115  CTNNA1; catenin alpha-1 [KO:K05691]
114502549  junction plakoglobin [KO:K10056]
114507737  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
114507559  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
114510422  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
114502553  FGF2; fibroblast growth factor 2 [KO:K18497]
114509809  FGF18; fibroblast growth factor 18 [KO:K04358]
114496691  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
114503602  FGF22; LOW QUALITY PROTEIN: fibroblast growth factor 22 [KO:K04358]
114504014  FGF17; fibroblast growth factor 17 [KO:K04358]
114512610  FGF6; fibroblast growth factor 6 [KO:K04358]
114491712  FGF7; fibroblast growth factor 7 [KO:K04358]
114499168  FGF3; fibroblast growth factor 3 [KO:K04358]
114505270  FGF16; fibroblast growth factor 16 [KO:K04358]
114514054  FGF9; fibroblast growth factor 9 [KO:K04358]
114493120  FGF5; fibroblast growth factor 5 [KO:K04358]
114500857  FGF4; fibroblast growth factor 4 [KO:K04358]
114501717  FGF10; fibroblast growth factor 10 [KO:K04358]
114508944  FGF20; fibroblast growth factor 20 [KO:K04358]
114499167  FGF19; fibroblast growth factor 19 [KO:K22603]
114510830  FGF21; fibroblast growth factor 21 [KO:K22429]
114514005  FGF23; fibroblast growth factor 23 [KO:K22428]
114496712  FGFR2; fibroblast growth factor receptor 2 isoform X8 [KO:K05093] [EC:2.7.10.1]
114503125  GAB1; GRB2-associated-binding protein 1 isoform X4 [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
pdic04010  MAPK signaling pathway
pdic04110  Cell cycle
pdic04115  p53 signaling pathway
pdic04151  PI3K-Akt signaling pathway
pdic04310  Wnt signaling pathway
pdic04350  TGF-beta signaling pathway
pdic04520  Adherens junction
KO pathway
ko05226   
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