KEGG   PATHWAY: mcal05226
Entry
mcal05226                   Pathway                                
Name
Gastric cancer - Mus caroli (Ryukyu mouse)
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
mcal05226  Gastric cancer
mcal05226

Organism
Mus caroli (Ryukyu mouse) [GN:mcal]
Gene
110295211  Cdx2; homeobox protein CDX-2 isoform X1 [KO:K22234]
110298090  Muc2; mucin-2 [KO:K10955]
110293216  Cdh17; cadherin-17 [KO:K06811]
110290571  Reg4; regenerating islet-derived protein 4 [KO:K22244]
110295101  Abcb1; multidrug resistance protein 1 [KO:K05658] [EC:7.6.2.2]
110294612  Shh; sonic hedgehog protein isoform X1 [KO:K11988]
110305297  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110283679  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
110303739  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110296344  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
110308191  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110297919  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
110283660  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
110290093  Ddb2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
110308520  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
110309199  Rarb; retinoic acid receptor beta isoform X2 [KO:K08528]
110308122  Rxra; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
110312146  Rxrb; retinoic acid receptor RXR-beta isoform X3 [KO:K08525]
110290588  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
110310964  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
110296313  Wnt2; protein Wnt-2 [KO:K00182]
110291476  Wnt2b; protein Wnt-2b [KO:K00182]
110305853  Wnt3a; protein Wnt-3a [KO:K00312]
110304911  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
110293218  Wnt4; protein Wnt-4 isoform X1 [KO:K00408]
110295760  Wnt5b; protein Wnt-5b [KO:K00444]
110309360  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
110299810  Wnt6; protein Wnt-6 [KO:K00445]
110310689  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
110296669  Wnt7a; protein Wnt-7a isoform X1 [KO:K00572]
110285759  Wnt8b; protein Wnt-8b [KO:K00714]
110285093  Wnt8a; protein Wnt-8a [KO:K00714]
110306039  Wnt9a; protein Wnt-9a [KO:K01064]
110305968  Wnt9b; protein Wnt-9b [KO:K01064]
110310912  Wnt10b; protein Wnt-10b isoform X1 [KO:K01357]
110300434  Wnt10a; protein Wnt-10a [KO:K01357]
110298907  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
110296883  Wnt16; protein Wnt-16 [KO:K01558]
110301431  Fzd7; frizzled-7 [KO:K02432]
110294363  Fzd1; frizzled-1 [KO:K02432]
110305336  Fzd2; frizzled-2 [KO:K02235]
110309352  Fzd3; frizzled-3 [KO:K02329]
110298417  Fzd4; frizzled-4 [KO:K02354]
110294401  Fzd5; frizzled-5 [KO:K02375]
110284745  Fzd8; frizzled-8 [KO:K02375]
110310580  Fzd6; frizzled-6 [KO:K02376]
110295350  Fzd9; frizzled-9 [KO:K02842]
110295197  Fzd10; frizzled-10 [KO:K02842]
110286073  Lrp5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
110297114  Lrp6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
110292264  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
110304161  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
110311604  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
110299413  proto-oncogene FRAT1-like [KO:K03069]
110285589  Frat1; proto-oncogene FRAT1 [KO:K03069]
110285818  Frat2; GSK-3-binding protein FRAT2 [KO:K03096]
110311365  Gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
110284040  Axin1; axin-1 isoform X1 [KO:K02157]
110304669  Axin2; axin-2 [KO:K04385]
110284455  Apc; adenomatous polyposis coli protein isoform X4 [KO:K02085]
110303367  Apc2; adenomatous polyposis coli protein 2 isoform X2 [KO:K02085]
110301052  Ctnnb1; catenin beta-1 [KO:K02105]
110284498  Csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
110304948  Tcf7; transcription factor 7 isoform X2 [KO:K02620]
110296038  Tcf7l1; transcription factor 7-like 1 isoform X2 [KO:K04490]
110285273  Tcf7l2; transcription factor 7-like 2 isoform X5 [KO:K04491]
110290892  Lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
110310583  Myc; myc proto-oncogene protein [KO:K04377]
110298189  Ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
110307847  Tert; telomerase reverse transcriptase isoform X2 [KO:K11126] [EC:2.7.7.49]
110291005  Egf; pro-epidermal growth factor isoform X1 [KO:K04357]
110304228  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
110304771  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
110290710  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
110303444  Shc2; SHC-transforming protein 2 [KO:K17447]
110308134  Shc3; SHC-transforming protein 3 [KO:K17448]
110289726  Shc4; SHC-transforming protein 4 [KO:K17449]
110304772  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
110306968  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110312423  Sos1; son of sevenless homolog 1 [KO:K03099]
110297313  Hras; GTPase HRas isoform X2 [KO:K02833]
110296194  Kras; GTPase KRas isoform X1 [KO:K07827]
110290873  Nras; GTPase NRas [KO:K07828]
110287540  Araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
110295945  Braf; serine/threonine-protein kinase B-raf isoform X5 [KO:K04365] [EC:2.7.11.1]
110296919  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110301502  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110303196  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110297836  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110311382  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
110290798  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110292183  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110301355  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
110308009  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110299855  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
110292624  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
110297609  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110294471  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110307022  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110292680  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110285417  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
110304919  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
110302433  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110301878  Mlh1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
110296846  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
110303221  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
110292124  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
110298604  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
110309179  Rb1; retinoblastoma-associated protein [KO:K06618]
110289983  E2f1; transcription factor E2F1 [KO:K17454]
110293508  E2f2; transcription factor E2F2 isoform X1 [KO:K09389]
110308034  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
110298438  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
110292955  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
110306834  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
110292408  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
110301725  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
110284497  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
110301346  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
110284933  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
110292822  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
110300286  Cdh1; cadherin-1 [KO:K05689]
110302662  Ctnna3; catenin alpha-3 isoform X1 [KO:K05691]
110284850  Ctnna1; catenin alpha-1 isoform X1 [KO:K05691]
110295850  Ctnna2; catenin alpha-2 isoform X1 [KO:K05691]
110305003  Jup; junction plakoglobin [KO:K10056]
110294216  Hgf; hepatocyte growth factor isoform X1 [KO:K05460]
110295947  Met; hepatocyte growth factor receptor isoform X2 [KO:K05099] [EC:2.7.10.1]
110284837  Fgf1; fibroblast growth factor 1 isoform X1 [KO:K18496]
110291557  Fgf2; fibroblast growth factor 2 [KO:K18497]
110300580  Fgf20; fibroblast growth factor 20 [KO:K04358]
110295342  Fgf5; fibroblast growth factor 5 isoform X1 [KO:K04358]
110285629  Fgf8; fibroblast growth factor 8 isoform X1 [KO:K04358]
110287226  Fgf16; fibroblast growth factor 16 [KO:K04358]
110305760  Fgf18; fibroblast growth factor 18 [KO:K04358]
110308847  Fgf17; fibroblast growth factor 17 isoform X1 [KO:K04358]
110303818  Fgf22; fibroblast growth factor 22 isoform X1 [KO:K04358]
110309422  Fgf9; fibroblast growth factor 9 [KO:K04358]
110289950  Fgf7; fibroblast growth factor 7 [KO:K04358]
110296943  Fgf6; fibroblast growth factor 6 [KO:K04358]
110299316  Fgf4; fibroblast growth factor 4 [KO:K04358]
110299386  Fgf3; fibroblast growth factor 3 [KO:K04358]
110308330  Fgf10; fibroblast growth factor 10 [KO:K04358]
110299450  Fgf19; fibroblast growth factor 19 [KO:K22603]
110299358  Fgf21; fibroblast growth factor 21 [KO:K22429]
110297028  Fgf23; fibroblast growth factor 23 [KO:K22428]
110299396  Fgfr2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
110300068  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
mcal04010  MAPK signaling pathway
mcal04110  Cell cycle
mcal04115  p53 signaling pathway
mcal04151  PI3K-Akt signaling pathway
mcal04310  Wnt signaling pathway
mcal04350  TGF-beta signaling pathway
mcal04520  Adherens junction
KO pathway
ko05226   
LinkDB

DBGET integrated database retrieval system