KEGG   PATHWAY: rno05226
Entry
rno05226                    Pathway                                
Name
Gastric cancer - Rattus norvegicus (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
rno05226  Gastric cancer
rno05226

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
66019  Cdx2; homeobox protein CDX-2 [KO:K22234]
24572  Muc2; mucin-2 precursor [KO:K10955]
117048  Cdh17; cadherin-17 precursor [KO:K06811]
445583  Reg4; regenerating islet-derived protein 4 precursor [KO:K22244]
170913  Abcb1a; ATP binding cassette subfamily B member 1A [KO:K05658] [EC:7.6.2.2]
24646  Abcb1b; ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
29499  Shh; sonic hedgehog protein precursor [KO:K11988]
24842  Tp53; cellular tumor antigen p53 [KO:K04451]
114851  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
25112  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
291005  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
299626  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
24887  Bax; apoptosis regulator BAX [KO:K02159]
367149  Bax-ps1; apoptosis regulator BAX-like [KO:K02159]
681314  apoptosis regulator BAX-like [KO:K02159]
116502  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
100362121  Ddb2; DNA damage-binding protein 2 [KO:K10140]
171525  Polk; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
24706  Rarb; retinoic acid receptor beta [KO:K08528]
25271  Rxra; retinoic acid receptor RXR-alpha [KO:K08524]
361801  Rxrb; retinoic acid receptor RXR-beta [KO:K08525]
83574  Rxrg; retinoic acid receptor RXR-gamma [KO:K08526]
24881  Wnt1; proto-oncogene Wnt-1 precursor [KO:K03209]
116466  Wnt2b; protein Wnt-2b [KO:K00182]
114487  Wnt2; protein Wnt-2 precursor [KO:K00182]
24882  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
303181  Wnt3a; protein Wnt-3a precursor [KO:K00312]
84426  Wnt4; protein Wnt-4 precursor [KO:K00408]
64566  Wnt5a; protein Wnt-5a precursor [KO:K00444]
282582  Wnt5b; protein Wnt-5b precursor [KO:K00444]
316526  Wnt6; protein Wnt-6 precursor [KO:K00445]
114850  Wnt7a; protein Wnt-7a precursor [KO:K00572]
315196  Wnt7b; protein Wnt-7b isoform 1 [KO:K00572]
291678  Wnt8a; protein Wnt-8a precursor [KO:K00714]
293990  Wnt8b; protein Wnt-8b precursor [KO:K00714]
287357  Wnt9a; protein Wnt-9a precursor [KO:K01064]
303586  Wnt9b; protein Wnt-9b precursor [KO:K01064]
315294  Wnt10b; protein Wnt-10b precursor [KO:K01357]
316527  Wnt10a; protein Wnt-10a precursor [KO:K01357]
140584  Wnt11; protein Wnt-11 [KO:K01384]
500047  Wnt16; protein Wnt-16 precursor [KO:K01558]
58868  Fzd1; frizzled-1 precursor [KO:K02432]
100360552  Fzd7; frizzled-7 precursor [KO:K02432]
64512  Fzd2; frizzled-2 precursor [KO:K02235]
266715  Fzd3; frizzled-3 precursor [KO:K02329]
64558  Fzd4; frizzled-4 precursor [KO:K02354]
317674  Fzd5; frizzled-5 precursor [KO:K02375]
364754  Fzd8; frizzled-8 precursor [KO:K02375]
282581  Fzd6; frizzled-6 precursor [KO:K02376]
266608  Fzd9; frizzled-9 precursor [KO:K02842]
363913  Fzd10; frizzled-10 precursor [KO:K02842]
293649  Lrp5; low-density lipoprotein receptor-related protein 5 precursor [KO:K03068]
312781  Lrp6; low-density lipoprotein receptor-related protein 6 isoform 2 precursor [KO:K03068]
83721  Dvl1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
303811  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
303251  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
308692  Peg12; paternally expressed 12 [KO:K03069]
103691373  Frat1; proto-oncogene FRAT1 [KO:K03069]
679110  Frat2; GSK-3-binding protein FRAT2 [KO:K03096]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
79257  Axin1; axin-1 [KO:K02157]
29134  Axin2; axin-2 [KO:K04385]
24205  Apc; adenomatous polyposis coli protein [KO:K02085]
299611  Apc2; adenomatous polyposis coli protein 2 [KO:K02085]
84353  Ctnnb1; catenin beta-1 [KO:K02105]
113927  Csnk1a1; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
363595  Tcf7; transcription factor 7 [KO:K02620]
312451  Tcf7l1; transcription factor 7-like 1 [KO:K04490]
679869  Tcf7l2; transcription factor 7-like 2 [KO:K04491]
161452  Lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
24577  Myc; myc proto-oncogene protein [KO:K04377]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
301965  Tert; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
378461  Terc; telomerase RNA component [KO:K22183]
25313  Egf; pro-epidermal growth factor precursor [KO:K04357]
24329  Egfr; epidermal growth factor receptor isoform 2 precursor [KO:K04361] [EC:2.7.10.1]
24337  Erbb2; receptor tyrosine-protein kinase erbB-2 precursor [KO:K05083] [EC:2.7.10.1]
85385  Shc1; SHC-transforming protein 1 isoform b [KO:K06279]
314612  Shc2; SHC-transforming protein 2 [KO:K17447]
114858  Shc3; SHC-transforming protein 3 [KO:K17448]
679845  Shc4; SHC-transforming protein 4 [KO:K17449]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
293621  Hras; GTPase HRas [KO:K02833]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
64363  Araf; serine/threonine-protein kinase A-Raf isoform 1 [KO:K08845] [EC:2.7.11.1]
114486  Braf; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
56718  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
83840  Rps6kb1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
361696  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
81685  Mlh1; DNA mismatch repair protein Mlh1 [KO:K08734]
83571  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
362817  Cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
362485  Ccne2; G1/S-specific cyclin-E2 [KO:K06626]
25729  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
24708  Rb1; retinoblastoma-associated protein [KO:K06618]
399489  E2f1; transcription factor E2F1 [KO:K17454]
684111  E2f2; transcription factor E2F2 isoform X2 [KO:K09389]
59086  Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
81809  Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
25717  Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377]
29591  Tgfbr1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
81810  Tgfbr2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
29357  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
25631  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
50554  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
25164  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
83502  Cdh1; cadherin-1 precursor [KO:K05689]
307505  Ctnna1; catenin alpha-1 [KO:K05691]
297357  Ctnna2; catenin alpha-2 isoform 1 [KO:K05691]
81679  Jup; junction plakoglobin [KO:K10056]
24446  Hgf; hepatocyte growth factor preproprotein [KO:K05460]
24553  Met; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
25317  Fgf1; fibroblast growth factor 1 [KO:K18496]
54250  Fgf2; fibroblast growth factor 2 [KO:K18497]
170633  Fgf3; fibroblast growth factor 3 precursor [KO:K04358]
116499  Fgf4; fibroblast growth factor 4 precursor [KO:K04358]
60662  Fgf5; fibroblast growth factor 5 isoform 1 precursor [KO:K04358]
170700  Fgf6; fibroblast growth factor 6 [KO:K04358]
29348  Fgf7; fibroblast growth factor 7 precursor [KO:K04358]
25444  Fgf9; fibroblast growth factor 9 [KO:K04358]
25443  Fgf10; fibroblast growth factor 10 precursor [KO:K04358]
60464  Fgf16; fibroblast growth factor 16 [KO:K04358]
29368  Fgf17; fibroblast growth factor 17 isoform 1 precursor [KO:K04358]
29369  Fgf18; fibroblast growth factor 18 precursor [KO:K04358]
66017  Fgf20; fibroblast growth factor 20 [KO:K04358]
170579  Fgf22; fibroblast growth factor 22 precursor [KO:K04358]
170582  Fgf19; fibroblast growth factor 19 precursor [KO:K22603]
170580  Fgf21; fibroblast growth factor 21 precursor [KO:K22429]
170583  Fgf23; fibroblast growth factor 23 precursor [KO:K22428]
25022  Fgfr2; fibroblast growth factor receptor 2 isoform b [KO:K05093] [EC:2.7.10.1]
361388  Gab1; GRB2-associated-binding protein 1 [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
rno04010  MAPK signaling pathway
rno04110  Cell cycle
rno04115  p53 signaling pathway
rno04151  PI3K-Akt signaling pathway
rno04310  Wnt signaling pathway
rno04350  TGF-beta signaling pathway
rno04520  Adherens junction
KO pathway
ko05226   
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