KEGG   PATHWAY: dsp05226
Entry
dsp05226                    Pathway                                
Name
Gastric cancer - Dipodomys spectabilis (banner-tailed kangaroo rat)
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
dsp05226  Gastric cancer
dsp05226

Organism
Dipodomys spectabilis (banner-tailed kangaroo rat) [GN:dsp]
Gene
122112909  Cdx2; homeobox protein CDX-2 [KO:K22234]
122102710  mucin-2-like [KO:K10955]
122102363  Cdh17; cadherin-17 [KO:K06811]
122112632  Reg4; regenerating islet-derived protein 4 [KO:K22244]
122111774  Abcb1; ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
122111776  ATP-dependent translocase ABCB1-like [KO:K05658] [EC:7.6.2.2]
122105862  Shh; sonic hedgehog protein [KO:K11988]
122100440  Tp53; cellular tumor antigen p53 [KO:K04451]
122111380  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
122104319  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122113654  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122099301  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122125840  Bax; apoptosis regulator BAX [KO:K02159]
122111128  Bak1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
122104989  Ddb2; DNA damage-binding protein 2 [KO:K10140]
122117376  Polk; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
122108096  Rarb; retinoic acid receptor beta [KO:K08528]
122108988  Rxra; retinoic acid receptor RXR-alpha [KO:K08524]
122111094  Rxrb; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
122106072  Rxrg; retinoic acid receptor RXR-gamma [KO:K08526]
122106358  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
122104095  Wnt2b; protein Wnt-2b [KO:K00182]
122121825  Wnt2; protein Wnt-2 [KO:K00182]
122103469  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
122098964  Wnt3a; protein Wnt-3a [KO:K00312]
122115226  Wnt4; protein Wnt-4 [KO:K00408]
122099575  Wnt5b; LOW QUALITY PROTEIN: protein Wnt-5b [KO:K00444]
122108141  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
122107573  Wnt6; protein Wnt-6 [KO:K00445]
122096831  Wnt7b; protein Wnt-7b [KO:K00572]
122108198  Wnt7a; protein Wnt-7a [KO:K00572]
122115988  Wnt8b; protein Wnt-8b [KO:K00714]
122118246  Wnt8a; protein Wnt-8a [KO:K00714]
122103516  Wnt9b; protein Wnt-9b [KO:K01064]
122098938  Wnt9a; LOW QUALITY PROTEIN: protein Wnt-9a [KO:K01064]
122106350  Wnt10b; protein Wnt-10b [KO:K01357]
122107497  Wnt10a; protein Wnt-10a [KO:K01357]
122115365  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
122121786  Wnt16; protein Wnt-16 [KO:K01558]
122096462  Fzd7; frizzled-7 [KO:K02432]
122111920  Fzd1; frizzled-1 [KO:K02432]
122103290  Fzd2; frizzled-2 [KO:K02235]
122125249  Fzd3; frizzled-3 isoform X1 [KO:K02329]
122114819  Fzd4; frizzled-4 [KO:K02354]
122113306  Fzd8; frizzled-8 [KO:K02375]
122107578  Fzd5; frizzled-5 [KO:K02375]
122102404  Fzd6; frizzled-6 [KO:K02376]
122113827  Fzd9; frizzled-9 [KO:K02842]
122098849  Fzd10; frizzled-10 [KO:K02842]
122104921  Lrp5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
122101230  Lrp6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
122127322  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
122096769  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
122100418  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
122115816  Frat1; proto-oncogene FRAT1 [KO:K03069]
122115797  Frat2; GSK-3-binding protein FRAT2 [KO:K03096]
122096813  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
122098148  Axin1; axin-1 isoform X1 [KO:K02157]
122094958  Axin2; axin-2 [KO:K04385]
122122822  Apc2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
122118219  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
122124883  Ctnnb1; catenin beta-1 [KO:K02105]
122121043  casein kinase I-like isoform X1 [KO:K08957] [EC:2.7.11.1]
122113719  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
122113956  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
122118200  Csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
122115432  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
122116902  Tcf7l1; transcription factor 7-like 1 [KO:K04490]
122115716  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
122127220  Lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
122102408  Myc; myc proto-oncogene protein [KO:K04377]
122099882  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
122121024  Tert; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
122127051  Egf; pro-epidermal growth factor [KO:K04357]
122112209  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
122103204  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
122109169  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
122122823  Shc2; SHC-transforming protein 2 [KO:K17447]
122113790  Shc3; SHC-transforming protein 3 [KO:K17448]
122114464  Shc4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449]
122128376  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
122104519  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
122106484  Sos2; son of sevenless homolog 2 [KO:K03099]
122095011  Hras; GTPase HRas isoform X1 [KO:K02833]
122098841  Kras; GTPase KRas isoform X1 [KO:K07827]
122118367  Nras; GTPase NRas [KO:K07828]
122098764  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
122105936  Braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
122107826  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122114391  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122099331  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122095844  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122096287  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122095294  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122121501  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122107232  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122123339  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like [KO:K00922] [EC:2.7.1.153]
122108047  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122100872  Pik3r2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122117343  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122097416  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122101263  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122126696  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122121508  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
122105362  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
122117335  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
122119434  Bcl2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
122096100  Mlh1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
122101247  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
122124349  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
122097446  Ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
122102319  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
122112815  Rb1; retinoblastoma-associated protein [KO:K06618]
122120305  E2f1; transcription factor E2F1 isoform X1 [KO:K17454]
122115181  E2f2; transcription factor E2F2 isoform X1 [KO:K09389]
122107009  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
122097410  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
122109464  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
122118877  Tgfb3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
122121204  Tgfbr1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
122096026  Tgfbr2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
122104270  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
122114693  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
122104309  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
122118978  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
122126091  Cdh1; cadherin-1 [KO:K05689]
122122363  Ctnna3; catenin alpha-3 [KO:K05691]
122116860  Ctnna2; catenin alpha-2 isoform X1 [KO:K05691]
122118124  Ctnna1; catenin alpha-1 [KO:K05691]
122103314  junction plakoglobin [KO:K10056]
122111940  Hgf; hepatocyte growth factor isoform X1 [KO:K05460]
122121823  Met; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
122118224  Fgf1; fibroblast growth factor 1 [KO:K18496]
122119078  Fgf2; fibroblast growth factor 2 [KO:K18497]
122127554  Fgf20; fibroblast growth factor 20 [KO:K04358]
122096618  Fgf17; fibroblast growth factor 17 isoform X1 [KO:K04358]
122112831  Fgf9; fibroblast growth factor 9 [KO:K04358]
122097662  Fgf16; fibroblast growth factor 16 [KO:K04358]
122106885  Fgf5; fibroblast growth factor 5 [KO:K04358]
122114692  Fgf7; fibroblast growth factor 7 [KO:K04358]
122122838  Fgf22; fibroblast growth factor 22 [KO:K04358]
122099887  Fgf3; fibroblast growth factor 3 [KO:K04358]
122115956  Fgf8; fibroblast growth factor 8 isoform X1 [KO:K04358]
122101870  Fgf18; fibroblast growth factor 18 [KO:K04358]
122117016  Fgf10; fibroblast growth factor 10 [KO:K04358]
122102809  Fgf6; LOW QUALITY PROTEIN: fibroblast growth factor 6 [KO:K04358]
122125586  Fgf21; fibroblast growth factor 21 [KO:K22429]
122102807  Fgf23; fibroblast growth factor 23 [KO:K22428]
122126852  Fgfr2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
122127211  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
dsp04010  MAPK signaling pathway
dsp04110  Cell cycle
dsp04115  p53 signaling pathway
dsp04151  PI3K-Akt signaling pathway
dsp04310  Wnt signaling pathway
dsp04350  TGF-beta signaling pathway
dsp04520  Adherens junction
KO pathway
ko05226   
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