KEGG   PATHWAY: cpoc05226
Entry
cpoc05226                   Pathway                                
Name
Gastric cancer - Cavia porcellus (domestic guinea pig)
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
cpoc05226  Gastric cancer
cpoc05226

Organism
Cavia porcellus (domestic guinea pig) [GN:cpoc]
Gene
100720187  Cdx2; homeobox protein CDX-2 isoform X1 [KO:K22234]
100718080  Cdh17; cadherin-17 [KO:K06811]
100727547  Reg4; regenerating islet-derived protein 4 [KO:K22244]
100732684  multidrug resistance protein 1-like [KO:K05658] [EC:7.6.2.2]
100733532  Abcb1; multidrug resistance protein 1 [KO:K05658] [EC:7.6.2.2]
100732014  Shh; sonic hedgehog protein [KO:K11988]
100379269  Tp53; cellular tumor antigen p53 [KO:K04451]
100720449  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100719739  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100730773  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100730890  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
100734553  Bak1; bcl-2 homologous antagonist/killer isoform X2 [KO:K14021]
100726538  Ddb2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100726233  Polk; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
100379264  Rarb; retinoic acid receptor beta [KO:K08528]
100728437  Rxra; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
100732959  Rxrb; retinoic acid receptor RXR-beta isoform X2 [KO:K08525]
100731736  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
100717026  Wnt1; LOW QUALITY PROTEIN: proto-oncogene Wnt-1 [KO:K03209]
100714996  Wnt2b; protein Wnt-2b [KO:K00182]
100719346  Wnt2; protein Wnt-2 [KO:K00182]
100726694  Wnt3a; protein Wnt-3a [KO:K00312]
100734613  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
100724855  Wnt4; protein Wnt-4 isoform X1 [KO:K00408]
100715484  Wnt5b; protein Wnt-5b isoform X2 [KO:K00444]
100723890  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
100713618  Wnt6; protein Wnt-6 [KO:K00445]
100726062  Wnt7b; protein Wnt-7b [KO:K00572]
100719106  Wnt7a; protein Wnt-7a [KO:K00572]
100725534  Wnt8a; protein Wnt-8a [KO:K00714]
100724403  Wnt8b; protein Wnt-8b [KO:K00714]
100726329  Wnt9a; protein Wnt-9a [KO:K01064]
100729157  Wnt9b; protein Wnt-9b [KO:K01064]
100713337  Wnt10a; protein Wnt-10a [KO:K01357]
100728910  Wnt10b; protein Wnt-10b [KO:K01357]
100718108  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
100721822  Wnt16; protein Wnt-16 [KO:K01558]
100735394  Fzd7; frizzled-7 [KO:K02432]
100730489  Fzd1; LOW QUALITY PROTEIN: frizzled-1 [KO:K02432]
100726820  Fzd2; frizzled-2 [KO:K02235]
100716417  Fzd3; LOW QUALITY PROTEIN: frizzled-3 [KO:K02329]
100714941  Fzd4; frizzled-4 [KO:K02354]
100728348  Fzd5; frizzled-5 [KO:K02375]
100719748  Fzd6; LOW QUALITY PROTEIN: frizzled-6 [KO:K02376]
100735834  Fzd9; frizzled-9 [KO:K02842]
100731601  Fzd10; frizzled-10 [KO:K02842]
100714196  Lrp5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
100735282  Lrp6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
100728748  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
100717450  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
100723761  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
101789016  Frat2; LOW QUALITY PROTEIN: GSK-3-binding protein FRAT2 [KO:K03096]
100714392  Gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100718536  Axin1; axin-1 isoform X1 [KO:K02157]
100731715  Axin2; axin-2 isoform X1 [KO:K04385]
100723694  Apc; adenomatous polyposis coli protein isoform X2 [KO:K02085]
100735498  Apc2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
100732604  Ctnnb1; catenin beta-1 [KO:K02105]
100724050  Csnk1a1; casein kinase I isoform X3 [KO:K08957] [EC:2.7.11.1]
100712802  Tcf7; transcription factor 7 [KO:K02620]
100731379  Tcf7l1; transcription factor 7-like 1 [KO:K04490]
100715721  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
100716066  Lef1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100724557  Myc; myc proto-oncogene protein isoform X2 [KO:K04377]
100729808  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
100732437  Tert; LOW QUALITY PROTEIN: telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
100714471  Egf; pro-epidermal growth factor isoform X1 [KO:K04357]
100725363  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100727657  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
100734561  Shc1; SHC-transforming protein 1 isoform X2 [KO:K06279]
100723025  SHC-transforming protein 2 [KO:K17447]
100732336  Shc3; SHC-transforming protein 3 [KO:K17448]
100717842  Shc4; SHC-transforming protein 4 [KO:K17449]
100715453  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
100721165  Sos1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
100726398  Sos2; son of sevenless homolog 2 [KO:K03099]
100735038  Hras; GTPase HRas isoform X1 [KO:K02833]
100716262  Kras; GTPase KRas isoform X3 [KO:K07827]
100135584  Nras; GTPase NRas [KO:K07828]
100727629  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
100717765  Braf; LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
100720110  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
100712888  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
100728923  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100715180  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100725692  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100720622  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100727986  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100735084  Pik3ca; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100734206  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100730242  Pik3r1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100734044  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100719925  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100714724  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100724315  Akt3; LOW QUALITY PROTEIN: RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100724938  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100727216  Rps6kb1; LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
100722430  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100733337  Bcl2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
100717848  Mlh1; DNA mismatch repair protein Mlh1 isoform X2 [KO:K08734]
100729359  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100714324  Cdk2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
100734034  Ccne2; G1/S-specific cyclin-E2 [KO:K06626]
100727568  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
100716297  Rb1; LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]
100729531  E2f1; transcription factor E2F1 [KO:K17454]
100714679  E2f2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
100722981  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
100135628  Tgfb1; transforming growth factor beta-1 precursor [KO:K13375]
100720726  Tgfb2; transforming growth factor beta-2 isoform X3 [KO:K13376]
100715426  Tgfb3; transforming growth factor beta-3 [KO:K13377]
100715237  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100718284  Tgfbr2; TGF-beta receptor type-2 isoform X3 [KO:K04388] [EC:2.7.11.30]
100726958  Smad2; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 2 [KO:K04500]
100731807  Smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100717853  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100732246  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100726210  Cdh1; cadherin-1 [KO:K05689]
100720469  Ctnna1; LOW QUALITY PROTEIN: catenin alpha-1 [KO:K05691]
100730912  catenin alpha-2 [KO:K05691]
100729463  Ctnna3; catenin alpha-3 isoform X1 [KO:K05691]
100714103  Jup; junction plakoglobin [KO:K10056]
100730730  Hgf; hepatocyte growth factor isoform X1 [KO:K05460]
100718790  Met; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
100727152  Fgf1; fibroblast growth factor 1 isoform X2 [KO:K18496]
100721182  Fgf2; fibroblast growth factor 2 isoform X1 [KO:K18497]
100722934  Fgf5; fibroblast growth factor 5 isoform X2 [KO:K04358]
100730085  Fgf10; fibroblast growth factor 10 [KO:K04358]
100723648  Fgf16; fibroblast growth factor 16 [KO:K04358]
100730876  Fgf6; fibroblast growth factor 6 [KO:K04358]
100727356  Fgf17; fibroblast growth factor 17 isoform X1 [KO:K04358]
100718957  Fgf7; fibroblast growth factor 7 [KO:K04358]
100715152  Fgf18; fibroblast growth factor 18 [KO:K04358]
100732836  Fgf20; LOW QUALITY PROTEIN: fibroblast growth factor 20 [KO:K04358]
100727609  Fgf9; fibroblast growth factor 9 [KO:K04358]
100716446  Fgf3; fibroblast growth factor 3 [KO:K04358]
100730350  Fgf4; fibroblast growth factor 4 [KO:K04358]
100721186  Fgf22; fibroblast growth factor 22 [KO:K04358]
100728398  Fgf21; fibroblast growth factor 21 [KO:K22429]
100717518  Fgf23; fibroblast growth factor 23 [KO:K22428]
100379152  Fgfr2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
100730023  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
cpoc04010  MAPK signaling pathway
cpoc04110  Cell cycle
cpoc04115  p53 signaling pathway
cpoc04151  PI3K-Akt signaling pathway
cpoc04310  Wnt signaling pathway
cpoc04350  TGF-beta signaling pathway
cpoc04520  Adherens junction
KO pathway
ko05226   
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