KEGG   PATHWAY: ssc05226
Entry
ssc05226                    Pathway                                
Name
Gastric cancer - Sus scrofa (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
ssc05226  Gastric cancer
ssc05226

Disease
H00018  Gastric cancer
Organism
Sus scrofa (pig) [GN:ssc]
Gene
100038019  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100048953  CDH1; cadherin-1 precursor [KO:K05689]
100049703  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100126276  WNT10B; protein Wnt-10b precursor [KO:K01357]
100126852  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
100126861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100127132  CDX2; homeobox protein CDX-2 [KO:K22234]
100127145  MUC2; LOW QUALITY PROTEIN: mucin-2 [KO:K10955]
100127158  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100127359  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100127478  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100151828  RB1; retinoblastoma-associated protein [KO:K06618]
100152116  FGF6; fibroblast growth factor 6 [KO:K04358]
100152215  CDKN1A; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1 [KO:K06625]
100152223  FGF16; fibroblast growth factor 16 [KO:K04358]
100152997  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100153078  FZD3; frizzled-3 isoform X1 [KO:K02329]
100153445  WNT7A; protein Wnt-7a [KO:K00572]
100153846  E2F1; transcription factor E2F1 [KO:K17454]
100153922  TCF7L2; transcription factor 7-like 2 isoform X26 [KO:K04491]
100153927  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100153974  CTNNA3; catenin alpha-3 isoform X7 [KO:K05691]
100154407  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100154580  REG4; regenerating islet-derived protein 4 precursor [KO:K22244]
100154715  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100155304  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
100155339  FGF23; fibroblast growth factor 23 [KO:K22428]
100155720  FGF17; fibroblast growth factor 17 [KO:K04358]
100156242  FGF8; LOW QUALITY PROTEIN: fibroblast growth factor 8 [KO:K04358]
100156321  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
100156602  SOS2; son of sevenless homolog 2 [KO:K03099]
100156801  RXRB; retinoic acid receptor RXR-beta [KO:K08525]
100157360  FZD6; frizzled-6 precursor [KO:K02376]
100157834  CDH17; cadherin-17 [KO:K06811]
100170126  LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
100192436  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100233191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100302504  FGF21; fibroblast growth factor 21 precursor [KO:K22429]
100327037  WNT4; protein Wnt-4 [KO:K00408]
100337665  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
100337669  FZD2; frizzled-2 precursor [KO:K02235]
100511026  GAB1; LOW QUALITY PROTEIN: GRB2-associated-binding protein 1 [KO:K09593]
100511484  WNT16; protein Wnt-16 [KO:K01558]
100511782  FZD10; frizzled-10 [KO:K02842]
100511937  [KO:K02649]
100512048  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
100512153  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100512749  SHH; sonic hedgehog protein preproprotein [KO:K11988]
100512949  WNT9A; protein Wnt-9a [KO:K01064]
100512951  TCF7; transcription factor 7 isoform X1 [KO:K02620]
100513197  DDB2; DNA damage-binding protein 2 isoform X2 [KO:K10140]
100513655  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
100513672  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
100513691  FZD7; frizzled-7 [KO:K02432]
100513811  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100514516  CSNK1A1; casein kinase I isoform X4 [KO:K08957] [EC:2.7.11.1]
100514612  BRAF; serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:2.7.11.1]
100514950  WNT3A; protein Wnt-3a isoform X1 [KO:K00312]
100515777  LRP6; LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 6 [KO:K03068]
100516268  WNT5B; LOW QUALITY PROTEIN: protein Wnt-5b [KO:K00444]
100516301  FGF20; fibroblast growth factor 20 [KO:K04358]
100516641  ERBB2; receptor tyrosine-protein kinase erbB-2 precursor [KO:K05083] [EC:2.7.10.1]
100516839  WNT2; protein Wnt-2 [KO:K00182]
100517932  APC; adenomatous polyposis coli protein [KO:K02085]
100518131  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100518251  KRAS; GTPase KRas isoform X2 [KO:K07827]
100518595  FGF4; fibroblast growth factor 4 [KO:K04358]
100518650  POLK; LOW QUALITY PROTEIN: DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
100518950  FGF19; fibroblast growth factor 19 [KO:K22603]
100519058  FZD5; frizzled-5 [KO:K02375]
100519127  FGF3; fibroblast growth factor 3 [KO:K04358]
100519512  WNT3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
100520187  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100520319  FZD4; LOW QUALITY PROTEIN: frizzled-4 [KO:K02354]
100520560  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
100521912  WNT11; protein Wnt-11 [KO:K01384]
100522267  [KO:K05658] [EC:7.6.2.2]
100522455  [KO:K05658] [EC:7.6.2.2]
100523248  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100523725  AXIN1; axin-1 isoform X1 [KO:K02157]
100523778  CTNNA1; catenin alpha-1 [KO:K05691]
100523899  TCF7L1; LOW QUALITY PROTEIN: transcription factor 7-like 1 [KO:K04490]
100524299  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
100525013  FGF18; fibroblast growth factor 18 isoform X2 [KO:K04358]
100525086  FGF10; fibroblast growth factor 10 [KO:K04358]
100525120  HGF; hepatocyte growth factor isoform X3 [KO:K05460]
100525170  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
100525337  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
100525462  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100525505  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100526147  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
100579172  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
100621038  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100621090  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100621789  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100622044  WNT6; protein Wnt-6 [KO:K00445]
100622559  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100623646  WNT10A; LOW QUALITY PROTEIN: protein Wnt-10a [KO:K01357]
100623707  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100625452  DVL2; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
100625784  FZD9; frizzled-9 [KO:K02842]
100626947  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
100627056  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100737448  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100738589  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100738655  WNT9B; protein Wnt-9b [KO:K01064]
100739349  NRAS; GTPase NRas precursor [KO:K07828]
100739510  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100739604  AXIN2; axin-2 isoform X1 [KO:K04385]
100739710  WNT8A; protein Wnt-8a [KO:K00714]
102164918  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
110255708  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
110256598  FRAT1; proto-oncogene FRAT1 [KO:K03069]
110256599  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
110259208  HRAS; GTPase HRas isoform X1 [KO:K02833]
110259378  FGF22; fibroblast growth factor 22 [KO:K04358]
110259382  SHC2; SHC-transforming protein 2 [KO:K17447]
110261113  E2F2; transcription factor E2F2 [KO:K09389]
110262227  FZD1; frizzled-1 [KO:K02432]
396633  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
396665  TGFBR1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
396710  RARB; LOW QUALITY PROTEIN: retinoic acid receptor beta [KO:K08528]
396717  FGF9; fibroblast growth factor 9 [KO:K04358]
396762  FGFR2; fibroblast growth factor receptor 2 precursor [KO:K05093] [EC:2.7.10.1]
396910  ABCB1; ATP-binding cassette, sub-family B (MDR/TAP), member 1 [KO:K05658] [EC:7.6.2.2]
397070  EGFR; epidermal growth factor receptor precursor [KO:K04361] [EC:2.7.10.1]
397078  TGFB1; transforming growth factor beta-1 precursor [KO:K13375]
397083  EGF; pro-epidermal growth factor precursor [KO:K04357]
397084  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
397142  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
397227  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
397260  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
397276  TP53; cellular tumor antigen p53 [KO:K04451]
397281  FGF7; fibroblast growth factor 7 [KO:K04358]
397306  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
397400  TGFB3; transforming growth factor beta-3 precursor [KO:K13377]
397497  FGF1; fibroblast growth factor 1 [KO:K18496]
397543  BAK1; bcl-2 homologous antagonist/killer isoform X2 [KO:K14021]
397584  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
397592  JUP; junction plakoglobin [KO:K10056]
397601  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
397643  FGF2; fibroblast growth factor 2 [KO:K18497]
397657  CTNNB1; catenin beta-1 [KO:K02105]
445013  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
445465  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
448810  MYC; myc proto-oncogene protein [KO:K04377]
492280  TERT; telomerase reverse transcriptase [KO:K11126] [EC:2.7.7.49]
654328  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
733669  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
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
ssc04010  MAPK signaling pathway
ssc04110  Cell cycle
ssc04115  p53 signaling pathway
ssc04151  PI3K-Akt signaling pathway
ssc04310  Wnt signaling pathway
ssc04350  TGF-beta signaling pathway
ssc04520  Adherens junction
KO pathway
ko05226   

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