KEGG   PATHWAY: sbq05226
Entry
sbq05226                    Pathway                                
Name
Gastric cancer - Saimiri boliviensis boliviensis (Bolivian squirrel monkey)
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
sbq05226  Gastric cancer
sbq05226

Organism
Saimiri boliviensis boliviensis (Bolivian squirrel monkey) [GN:sbq]
Gene
101037292  CDX2; homeobox protein CDX-2 [KO:K22234]
101031458  MUC2; mucin-2 [KO:K10955]
101039647  CDH17; cadherin-17 [KO:K06811]
101043543  REG4; regenerating islet-derived protein 4 [KO:K22244]
101052405  ABCB1; multidrug resistance protein 1 [KO:K05658] [EC:7.6.2.2]
101034605  SHH; sonic hedgehog protein [KO:K11988]
101043647  TP53; cellular tumor antigen p53 [KO:K04451]
101041919  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
101030208  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101039106  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101047513  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101050177  BAX; apoptosis regulator BAX [KO:K02159]
101041291  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
101027903  DDB2; DNA damage-binding protein 2 isoform X2 [KO:K10140]
101034259  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
101053144  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
101044148  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
101040304  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
101040247  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
101044133  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101037307  WNT2; protein Wnt-2 [KO:K00182]
101051098  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
101035500  WNT3A; protein Wnt-3a [KO:K00312]
101048838  WNT3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
101050255  WNT4; protein Wnt-4 [KO:K00408]
101038250  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
101040063  WNT5A; protein Wnt-5a isoform X2 [KO:K00444]
101028364  WNT6; protein Wnt-6 [KO:K00445]
101027644  WNT7A; protein Wnt-7a [KO:K00572]
101041057  WNT8B; protein Wnt-8b [KO:K00714]
101037830  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
104650180  WNT9B; protein Wnt-9b [KO:K01064]
101029432  WNT10A; protein Wnt-10a [KO:K01357]
101043819  WNT10B; protein Wnt-10b [KO:K01357]
101050295  WNT11; protein Wnt-11 [KO:K01384]
101032778  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
101030044  FZD1; frizzled-1 [KO:K02432]
101049451  FZD7; frizzled-7 [KO:K02432]
101046720  FZD2; frizzled-2 [KO:K02235]
101037304  FZD3; frizzled-3 [KO:K02329]
101054300  FZD4; frizzled-4 [KO:K02354]
101036058  FZD5; frizzled-5 [KO:K02375]
101047742  FZD6; frizzled-6 [KO:K02376]
101030134  FZD9; frizzled-9 [KO:K02842]
101032028  FZD10; frizzled-10 [KO:K02842]
101045022  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
101054518  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
101035529  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
101028835  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
101044711  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
101053270  FRAT1; proto-oncogene FRAT1 [KO:K03069]
101051107  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
101035780  AXIN1; axin-1 isoform X2 [KO:K02157]
101036328  AXIN2; axin-2 isoform X1 [KO:K04385]
101034942  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
101049516  adenomatous polyposis coli protein isoform X1 [KO:K02085]
101043327  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
101037076  CSNK1A1; casein kinase I isoform alpha isoform X1 [KO:K08957] [EC:2.7.11.1]
101036015  CSNK1A1L; casein kinase I isoform alpha-like [KO:K08957] [EC:2.7.11.1]
101029076  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
101033762  TCF7L1; transcription factor 7-like 1 [KO:K04490]
101037011  TCF7L2; transcription factor 7-like 2 [KO:K04491]
101047688  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
101047066  MYC; myc proto-oncogene protein isoform X2 [KO:K04377]
101047858  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
101033079  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
101052478  EGF; pro-epidermal growth factor [KO:K04357]
101047461  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
101043415  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X2 [KO:K05083] [EC:2.7.10.1]
101038895  SHC1; SHC-transforming protein 1 [KO:K06279]
101047748  SHC-transforming protein 1 [KO:K06279]
101048523  SHC2; SHC-transforming protein 2 [KO:K17447]
101028764  SHC3; SHC-transforming protein 3 [KO:K17448]
101032627  SHC4; SHC-transforming protein 4 [KO:K17449]
101038666  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101036943  SOS1; son of sevenless homolog 1 [KO:K03099]
101046427  SOS2; son of sevenless homolog 2 [KO:K03099]
101047663  HRAS; GTPase HRas isoform X2 [KO:K02833]
101047035  KRAS; GTPase KRas isoform X1 [KO:K07827]
101036877  NRAS; GTPase NRas [KO:K07828]
101043605  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101052142  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
101054052  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101040361  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101036151  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101038546  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101043202  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101029768  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101052779  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101027982  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101032496  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101033359  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101050592  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101034861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101045714  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101040766  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101047083  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101033758  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
101038541  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101051366  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101028074  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
101030975  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101053477  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
101036684  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
101052282  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
101038309  RB1; retinoblastoma-associated protein [KO:K06618]
101029045  E2F1; transcription factor E2F1 [KO:K17454]
101042612  E2F2; transcription factor E2F2 [KO:K09389]
101034207  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
101047980  TGFB1; transforming growth factor beta-1 isoform X2 [KO:K13375]
101044624  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
101048819  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
101030583  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
101034142  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
101040653  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
101039593  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101032066  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101030939  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101049706  CDH1; cadherin-1 [KO:K05689]
101037437  CTNNA2; catenin alpha-2 isoform X4 [KO:K05691]
101030426  CTNNA3; catenin alpha-3 isoform X1 [KO:K05691]
101038365  CTNNA1; catenin alpha-1 isoform X1 [KO:K05691]
101049756  JUP; junction plakoglobin [KO:K10056]
101045517  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
101038696  MET; hepatocyte growth factor receptor isoform X2 [KO:K05099] [EC:2.7.10.1]
101040924  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
101030554  FGF2; fibroblast growth factor 2 [KO:K18497]
101048161  FGF8; fibroblast growth factor 8 [KO:K04358]
101040388  FGF20; fibroblast growth factor 20 [KO:K04358]
101040926  FGF17; fibroblast growth factor 17 isoform X2 [KO:K04358]
101047221  FGF4; fibroblast growth factor 4 [KO:K04358]
101046667  FGF18; fibroblast growth factor 18 [KO:K04358]
101046606  FGF10; fibroblast growth factor 10 [KO:K04358]
101042449  FGF3; fibroblast growth factor 3 [KO:K04358]
101048187  FGF6; fibroblast growth factor 6 [KO:K04358]
101052821  FGF9; fibroblast growth factor 9 [KO:K04358]
101031255  FGF7; fibroblast growth factor 7 [KO:K04358]
101050264  FGF16; fibroblast growth factor 16 [KO:K04358]
101031426  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
101047544  FGF19; fibroblast growth factor 19 [KO:K22603]
101048392  FGF21; fibroblast growth factor 21 [KO:K22429]
101048503  FGF23; fibroblast growth factor 23 [KO:K22428]
101033845  FGFR2; fibroblast growth factor receptor 2 isoform X11 [KO:K05093] [EC:2.7.10.1]
101040995  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
sbq04010  MAPK signaling pathway
sbq04110  Cell cycle
sbq04115  p53 signaling pathway
sbq04151  PI3K-Akt signaling pathway
sbq04310  Wnt signaling pathway
sbq04350  TGF-beta signaling pathway
sbq04520  Adherens junction
KO pathway
ko05226   
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