KEGG   PATHWAY: ko05226
Entry
ko05226                     Pathway                                
Name
Gastric cancer
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
ko05226  Gastric cancer
ko05226

Disease
H00018  Gastric cancer
Orthology
K00182  WNT2; wingless-type MMTV integration site family, member 2
K00312  WNT3; wingless-type MMTV integration site family, member 3
K00408  WNT4; wingless-type MMTV integration site family, member 4
K00444  WNT5; wingless-type MMTV integration site family, member 5
K00445  WNT6; wingless-type MMTV integration site family, member 6
K00572  WNT7; wingless-type MMTV integration site family, member 7
K00714  WNT8; wingless-type MMTV integration site family, member 8
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01064  WNT9; wingless-type MMTV integration site family, member 9
K01357  WNT10; wingless-type MMTV integration site family, member 10
K01384  WNT11; wingless-type MMTV integration site family, member 11
K01558  WNT16; wingless-type MMTV integration site family, member 16
K02085  APC; adenomatosis polyposis coli protein
K02105  CTNNB1; catenin beta 1
K02157  AXIN1; axin 1
K02159  BAX; apoptosis regulator BAX
K02161  BCL2; apoptosis regulator Bcl-2
K02206  CDK2; cyclin-dependent kinase 2 [EC:2.7.11.22]
K02235  FZD2; frizzled 2
K02329  FZD3; frizzled 3
K02353  DVL; segment polarity protein dishevelled
K02354  FZD4, fz4, CD344; frizzled 4
K02375  FZD5_8, fz2; frizzled 5/8
K02376  FZD6; frizzled 6
K02432  FZD1_7, fz; frizzled 1/7
K02620  TCF7, TCF-1; transcription factor 7
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02833  HRAS; GTPase HRas
K02842  FZD9_10, CD349_50; frizzled 9/10
K03068  LRP5_6; low density lipoprotein receptor-related protein 5/6
K03069  FRAT1; frequently rearranged in advanced T-cell lymphomas 1
K03083  GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03096  FRAT2; frequently rearranged in advanced T-cell lymphomas 2
K03099  SOS; son of sevenless
K03209  WNT1; wingless-type MMTV integration site family, member 1
K03511  POLK; DNA polymerase kappa [EC:2.7.7.7]
K04357  EGF; epidermal growth factor
K04358  FGF; fibroblast growth factor
K04361  EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]
K04364  GRB2; growth factor receptor-bound protein 2
K04365  BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04377  MYC; Myc proto-oncogene protein
K04385  AXIN2; axin 2
K04388  TGFBR2; TGF-beta receptor type-2 [EC:2.7.11.30]
K04402  GADD45; growth arrest and DNA-damage-inducible protein
K04451  TP53, P53; tumor protein p53
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04490  TCF7L1; transcription factor 7-like 1
K04491  TCF7L2; transcription factor 7-like 2
K04492  LEF1; lymphoid enhancer-binding factor 1
K04500  SMAD2; mothers against decapentaplegic homolog 2
K04501  SMAD4; mothers against decapentaplegic homolog 4
K04503  CCND1; G1/S-specific cyclin-D1
K04674  TGFBR1, ALK5; TGF-beta receptor type-1 [EC:2.7.11.30]
K04685  CDKN2B, P15, INK4B; cyclin-dependent kinase inhibitor 2B
K04688  RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1]
K05083  ERBB2, HER2, CD340; receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]
K05093  FGFR2, CD332; fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05099  MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05460  HGF; hepatocyte growth factor
K05658  ABCB1, CD243; ATP-binding cassette, subfamily B (MDR/TAP), member 1 [EC:7.6.2.2]
K05689  CDH1, CDHE, CD324; cadherin 1, type 1, E-cadherin
K05691  CTNNA; catenin alpha
K06279  SHC1; SHC-transforming protein 1
K06618  RB1; retinoblastoma-associated protein
K06620  E2F3; transcription factor E2F3
K06624  CDKN1B, P27, KIP1; cyclin-dependent kinase inhibitor 1B
K06625  CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K06626  CCNE; G1/S-specific cyclin-E1
K06811  CDH17; cadherin 17, LI cadherin
K07203  MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K08524  RXRA, NR2B1; retinoid X receptor alpha
K08525  RXRB, NR2B2; retinoid X receptor beta
K08526  RXRG, NR2B3; retinoid X receptor gamma
K08528  RARB, NR1B2; retinoic acid receptor beta
K08734  MLH1; DNA mismatch repair protein MLH1
K08845  ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K08957  CSNK1A; casein kinase 1, alpha [EC:2.7.11.1]
K09389  E2F2; transcription factor E2F2
K09593  GAB1; GRB2-associated-binding protein 1
K10056  JUP, PG; junction plakoglobin
K10140  DDB2; DNA damage-binding protein 2
K10955  MUC2; mucin-2
K11126  TERT, EST2; telomerase reverse transcriptase [EC:2.7.7.49]
K11988  SHH; sonic hedgehog
K13375  TGFB1; transforming growth factor beta-1
K13376  TGFB2; transforming growth factor beta-2
K13377  TGFB3; transforming growth factor beta-3
K14021  BAK, BAK1; Bcl-2 homologous antagonist/killer
K17447  SHC2; SHC-transforming protein 2
K17448  SHC3; SHC-transforming protein 3
K17449  SHC4; SHC-transforming protein 4
K17454  E2F1; transcription factor E2F1
K18496  FGF1; fibroblast growth factor 1
K18497  FGF2; fibroblast growth factor 2
K22183  TERC; telomerase RNA component
K22234  CDX2; homeobox protein CDX2
K22244  REG4; regenerating islet-derived protein 4
K22428  FGF23; fibroblast growth factor 23
K22429  FGF21; fibroblast growth factor 21
K22603  FGF19; fibroblast growth factor 19
K23605  SMAD3; mothers against decapentaplegic homolog 3
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
ko04010  MAPK signaling pathway
ko04110  Cell cycle
ko04115  p53 signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04310  Wnt signaling pathway
ko04350  TGF-beta signaling pathway
ko04520  Adherens junction
ko05120  Epithelial cell signaling in Helicobacter pylori infection

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