KEGG   PATHWAY: pkl05226
Entry
pkl05226                    Pathway                                
Name
Gastric cancer - Pipistrellus kuhlii (Kuhl's pipistrelle)
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
pkl05226  Gastric cancer
pkl05226

Organism
Pipistrellus kuhlii (Kuhl's pipistrelle) [GN:pkl]
Gene
118730082  CDX2; homeobox protein CDX-2 isoform X1 [KO:K22234]
118706930  MUC2; LOW QUALITY PROTEIN: mucin-2 [KO:K10955]
118718106  CDH17; cadherin-17 [KO:K06811]
118727133  REG4; regenerating islet-derived protein 4 isoform X1 [KO:K22244]
118714339  ABCB1; ATP-dependent translocase ABCB1 isoform X1 [KO:K05658] [EC:7.6.2.2]
118712271  SHH; sonic hedgehog protein [KO:K11988]
118726809  TP53; cellular tumor antigen p53 [KO:K04451]
118705573  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
118731305  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
118723504  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
118708686  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
118712174  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
118705679  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
118713534  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
118703506  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
118715411  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
118707032  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
118705657  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
118721741  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
118730320  WNT1; proto-oncogene Wnt-1 [KO:K03209]
118711791  WNT2; protein Wnt-2 [KO:K00182]
118727433  WNT2B; protein Wnt-2b [KO:K00182]
118726174  WNT3A; protein Wnt-3a [KO:K00312]
118726655  WNT3; proto-oncogene Wnt-3 [KO:K00312]
118723479  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
118729560  WNT5B; LOW QUALITY PROTEIN: protein Wnt-5b [KO:K00444]
118715112  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
118709830  WNT6; protein Wnt-6 [KO:K00445]
118724017  WNT7A; protein Wnt-7a [KO:K00572]
118708801  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
118711700  WNT8A; protein Wnt-8a [KO:K00714]
118719414  WNT8B; protein Wnt-8b [KO:K00714]
118725952  WNT9A; protein Wnt-9a [KO:K01064]
118726528  WNT9B; protein Wnt-9b [KO:K01064]
118730447  WNT10B; protein Wnt-10b [KO:K01357]
118709762  WNT10A; protein Wnt-10a isoform X1 [KO:K01357]
118713258  WNT11; protein Wnt-11 [KO:K01384]
118711976  WNT16; protein Wnt-16 [KO:K01558]
118714316  FZD1; frizzled-1 isoform X1 [KO:K02432]
118709964  FZD7; frizzled-7 isoform X1 [KO:K02432]
118726474  FZD2; frizzled-2 [KO:K02235]
118711082  FZD3; frizzled-3 isoform X1 [KO:K02329]
118712753  FZD4; frizzled-4 [KO:K02354]
118728313  FZD8; frizzled-8 [KO:K02375]
118709920  FZD5; frizzled-5 [KO:K02375]
118718151  FZD6; frizzled-6 isoform X1 [KO:K02376]
118702699  FZD9; frizzled-9 [KO:K02842]
118712500  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
118730116  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
118732013  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
118724342  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
118719347  FRAT1; proto-oncogene FRAT1 [KO:K03069]
118719349  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
118724168  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
118731609  AXIN1; axin-1 isoform X1 [KO:K02157]
118726414  AXIN2; LOW QUALITY PROTEIN: axin-2 [KO:K04385]
118711738  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
118703090  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
118715524  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
118720183  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118713409  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118721932  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118721960  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118709320  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118711053  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
118711309  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
118711889  TCF7; transcription factor 7 isoform X1 [KO:K02620]
118717604  TCF7L1; transcription factor 7-like 1 [KO:K04490]
118719486  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
118702904  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
118718671  MYC; myc proto-oncogene protein [KO:K04377]
118712764  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
118703495  TERT; telomerase reverse transcriptase isoform X1 [KO:K11126] [EC:2.7.7.49]
118702736  EGF; pro-epidermal growth factor [KO:K04357]
118727800  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
118702172  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
118721351  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
118711420  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
118708684  SHC3; SHC-transforming protein 3 [KO:K17448]
118721624  SHC4; SHC-transforming protein 4 [KO:K17449]
118704441  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
118717255  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
118718513  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
118717957  HRAS; GTPase HRas [KO:K02833]
118730853  KRAS; GTPase KRas isoform X1 [KO:K07827]
118727253  NRAS; GTPase NRas [KO:K07828]
118731760  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
118713842  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
118715231  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118731837  LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
118719104  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
118731359  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
118704886  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
118725266  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
118722506  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118715291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118731984  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118703803  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118722550  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
118725879  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
118727672  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118714856  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118702383  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118732041  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
118706947  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
118726541  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
118707440  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
118715474  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
118729119  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
118728263  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
118716047  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
118718119  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
118728588  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
118707945  E2F1; transcription factor E2F1 [KO:K17454]
118722322  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
118724618  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
118702316  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
118727653  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
118715108  transforming growth factor beta-3 proprotein [KO:K13377]
118715117  transforming growth factor beta-3 proprotein-like [KO:K13377]
118716264  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
118715431  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
118707412  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
118718916  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
118707871  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
118716636  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
118716727  LOW QUALITY PROTEIN: tumor suppressor ARF-like [KO:K04685]
118720916  CDH1; cadherin-1 isoform X1 [KO:K05689]
118711669  CTNNA1; catenin alpha-1 isoform X1 [KO:K05691]
118717594  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
118719189  CTNNA3; catenin alpha-3 [KO:K05691]
118726294  junction plakoglobin isoform X1 [KO:K10056]
118714360  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
118711705  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
118711036  FGF1; fibroblast growth factor 1 [KO:K18496]
118711281  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
118703459  FGF10; fibroblast growth factor 10 isoform X1 [KO:K04358]
118711796  FGF22; fibroblast growth factor 22 [KO:K04358]
118719938  FGF16; fibroblast growth factor 16 [KO:K04358]
118713262  FGF3; fibroblast growth factor 3 [KO:K04358]
118713563  FGF4; fibroblast growth factor 4 [KO:K04358]
118721585  FGF7; fibroblast growth factor 7 [KO:K04358]
118729747  FGF20; fibroblast growth factor 20 [KO:K04358]
118729964  FGF9; fibroblast growth factor 9 [KO:K04358]
118730618  FGF6; fibroblast growth factor 6 [KO:K04358]
118708533  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
118725847  FGF17; fibroblast growth factor 17 [KO:K04358]
118710939  FGF18; fibroblast growth factor 18 isoform X1 [KO:K04358]
118718923  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
118712851  FGF19; fibroblast growth factor 19 [KO:K22603]
118712172  FGF21; fibroblast growth factor 21 [KO:K22429]
118729553  FGF23; fibroblast growth factor 23 [KO:K22428]
118710524  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
118710767  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
pkl04010  MAPK signaling pathway
pkl04110  Cell cycle
pkl04115  p53 signaling pathway
pkl04151  PI3K-Akt signaling pathway
pkl04310  Wnt signaling pathway
pkl04350  TGF-beta signaling pathway
pkl04520  Adherens junction
KO pathway
ko05226   
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