KEGG   PATHWAY: aamp05226
Entry
aamp05226                   Pathway                                
Name
Gastric cancer - Arvicola amphibius (Eurasian water vole)
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
aamp05226  Gastric cancer
aamp05226

Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119825278  Cdx2; homeobox protein CDX-2 isoform X1 [KO:K22234]
119800609  Muc2; mucin-2 [KO:K10955]
119826566  Cdh17; cadherin-17 [KO:K06811]
119801406  Reg4; regenerating islet-derived protein 4 [KO:K22244]
119803921  ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
119803922  multidrug resistance protein 2 isoform X1 [KO:K05658] [EC:7.6.2.2]
119808182  Shh; LOW QUALITY PROTEIN: sonic hedgehog protein [KO:K11988]
119818608  cellular tumor antigen p53-like [KO:K04451]
119813419  Tp53; cellular tumor antigen p53 [KO:K04451]
119823049  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
119822349  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
119816942  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
119807493  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
119802627  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
119823918  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
119815700  Ddb2; DNA damage-binding protein 2 [KO:K10140]
119809608  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
119827403  Rarb; retinoic acid receptor beta isoform X1 [KO:K08528]
119818907  Rxra; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
119822749  Rxrb; retinoic acid receptor RXR-beta isoform X3 [KO:K08525]
119827442  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
119824043  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
119801133  Wnt2b; protein Wnt-2b [KO:K00182]
119807630  Wnt2; protein Wnt-2 [KO:K00182]
119813159  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
119817378  Wnt4; protein Wnt-4 [KO:K00408]
119827774  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
119808280  Wnt5b; protein Wnt-5b [KO:K00444]
119821641  Wnt6; protein Wnt-6 [KO:K00445]
119808152  Wnt7a; protein Wnt-7a [KO:K00572]
119823832  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
119801469  Wnt8b; protein Wnt-8b [KO:K00714]
119815317  Wnt8a; protein Wnt-8a [KO:K00714]
119812884  Wnt9b; protein Wnt-9b [KO:K01064]
119813175  Wnt9a; protein Wnt-9a [KO:K01064]
119821609  Wnt10a; protein Wnt-10a [KO:K01357]
119823873  Wnt10b; protein Wnt-10b [KO:K01357]
119802903  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
119808392  Wnt16; protein Wnt-16 [KO:K01558]
119803883  Fzd7; frizzled-7 [KO:K02432]
119803894  Fzd1; frizzled-1 [KO:K02432]
119813185  Fzd2; frizzled-2 [KO:K02235]
119800348  Fzd3; frizzled-3 [KO:K02329]
119802675  Fzd4; frizzled-4 [KO:K02354]
119802282  Fzd8; frizzled-8 [KO:K02375]
119820296  Fzd5; frizzled-5 [KO:K02375]
119822803  Fzd6; frizzled-6 [KO:K02376]
119825464  Fzd9; frizzled-9 [KO:K02842]
119825673  Fzd10; frizzled-10 [KO:K02842]
119825088  Lrp5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
119806598  Lrp6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
119816593  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
119811174  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
119824840  Dvl3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
119822495  Frat1; proto-oncogene FRAT1 [KO:K03069]
119822724  Frat2; GSK-3-binding protein FRAT2 [KO:K03096]
119824224  Gsk3b; LOW QUALITY PROTEIN: glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
119813237  Axin1; axin-1 isoform X1 [KO:K02157]
119813003  Axin2; axin-2 [KO:K04385]
119800867  Apc2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
119815778  Apc; adenomatous polyposis coli protein [KO:K02085]
119808978  Ctnnb1; catenin beta-1 [KO:K02105]
119814283  Csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
119812304  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
119807723  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
119806595  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
119800683  Lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
119822940  Myc; myc proto-oncogene protein [KO:K04377]
119827335  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
119810527  Tert; telomerase reverse transcriptase isoform X1 [KO:K11126] [EC:2.7.7.49]
119800992  Egf; pro-epidermal growth factor [KO:K04357]
119812357  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
119811725  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
119800744  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
119825434  Shc2; SHC-transforming protein 2 [KO:K17447]
119817129  Shc3; SHC-transforming protein 3 [KO:K17448]
119815646  Shc4; SHC-transforming protein 4 isoform X1 [KO:K17449]
119813014  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
119818434  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
119806329  Sos1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
119800249  Hras; GTPase HRas isoform X1 [KO:K02833]
119804230  GTPase KRas-like [KO:K07827]
119806318  Kras; GTPase KRas isoform X1 [KO:K07827]
119801497  Nras; GTPase NRas [KO:K07828]
119805132  Araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
119806667  Braf; LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
119808272  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
119805902  LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
119809903  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119827491  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
119824680  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119813356  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119816315  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119810503  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119826317  Pik3ca; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119808979  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119817743  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
119812102  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119818643  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119820487  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119827246  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119816408  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
119814876  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
119813254  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
119827718  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
119809006  Mlh1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
119807071  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
119803337  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
119820977  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
119804174  G1/S-specific cyclin-E2-like [KO:K06626]
119826163  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
119800094  Rb1; retinoblastoma-associated protein [KO:K06618]
119815142  E2f1; transcription factor E2F1 [KO:K17454]
119816691  E2f2; transcription factor E2F2 [KO:K09389]
119817711  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
119821456  Tgfb1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
119827432  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
119819138  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
119826264  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
119810460  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
119814613  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
119809845  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
119814141  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
119817430  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
119802116  Cdh1; cadherin-1 [KO:K05689]
119822763  Ctnna3; catenin alpha-3 [KO:K05691]
119806837  Ctnna2; catenin alpha-2 isoform X1 [KO:K05691]
119814100  Ctnna1; catenin alpha-1 [KO:K05691]
119813289  junction plakoglobin [KO:K10056]
119803884  Hgf; hepatocyte growth factor isoform X1 [KO:K05460]
119806540  Met; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
119814061  Fgf1; fibroblast growth factor 1 isoform X1 [KO:K18496]
119826229  Fgf2; fibroblast growth factor 2 [KO:K18497]
119800369  Fgf17; fibroblast growth factor 17 isoform X1 [KO:K04358]
119800397  Fgf9; fibroblast growth factor 9 [KO:K04358]
119814352  Fgf7; fibroblast growth factor 7 [KO:K04358]
119808412  Fgf6; fibroblast growth factor 6 [KO:K04358]
119808698  Fgf10; fibroblast growth factor 10 [KO:K04358]
119802892  Fgf22; fibroblast growth factor 22 isoform X1 [KO:K04358]
119812198  Fgf3; fibroblast growth factor 3 [KO:K04358]
119805412  Fgf16; fibroblast growth factor 16 [KO:K04358]
119825456  Fgf8; fibroblast growth factor 8 isoform X1 [KO:K04358]
119805928  Fgf5; fibroblast growth factor 5 [KO:K04358]
119805944  Fgf4; fibroblast growth factor 4 [KO:K04358]
119813362  Fgf20; fibroblast growth factor 20 [KO:K04358]
119806542  Fgf19; fibroblast growth factor 19 [KO:K22603]
119802871  Fgf21; fibroblast growth factor 21 [KO:K22429]
119807114  Fgf23; fibroblast growth factor 23 [KO:K22428]
119827742  Fgfr2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
119801830  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
aamp04010  MAPK signaling pathway
aamp04110  Cell cycle
aamp04115  p53 signaling pathway
aamp04151  PI3K-Akt signaling pathway
aamp04310  Wnt signaling pathway
aamp04350  TGF-beta signaling pathway
aamp04520  Adherens junction
KO pathway
ko05226   
LinkDB

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