KEGG   PATHWAY: ko05226
ko05226                     Pathway                                
Gastric cancer
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.
Human Diseases; Cancer: specific types
Pathway map
ko05226  Gastric cancer

H00018  Gastric cancer
K22234  homeobox protein CDX2
K10955  mucin-2
K06811  cadherin 17, LI cadherin
K22244  regenerating islet-derived protein 4
K05658  ATP-binding cassette, subfamily B (MDR/TAP), member 1 [EC:]
K11988  sonic hedgehog
K04451  tumor protein p53
K06625  cyclin-dependent kinase inhibitor 1A
K04402  growth arrest and DNA-damage-inducible protein
K02159  apoptosis regulator BAX
K14021  Bcl-2 homologous antagonist/killer
K10140  DNA damage-binding protein 2
K03511  DNA polymerase kappa [EC:]
K08528  retinoic acid receptor beta
K08524  retinoid X receptor alpha
K08525  retinoid X receptor beta
K08526  retinoid X receptor gamma
K03209  wingless-type MMTV integration site family, member 1
K00182  wingless-type MMTV integration site family, member 2
K00312  wingless-type MMTV integration site family, member 3
K00408  wingless-type MMTV integration site family, member 4
K00444  wingless-type MMTV integration site family, member 5
K00445  wingless-type MMTV integration site family, member 6
K00572  wingless-type MMTV integration site family, member 7
K00714  wingless-type MMTV integration site family, member 8
K01064  wingless-type MMTV integration site family, member 9
K01357  wingless-type MMTV integration site family, member 10
K01384  wingless-type MMTV integration site family, member 11
K01558  wingless-type MMTV integration site family, member 16
K02432  frizzled 1/7
K02235  frizzled 2
K02329  frizzled 3
K02354  frizzled 4
K02375  frizzled 5/8
K02376  frizzled 6
K02842  frizzled 9/10
K03068  low density lipoprotein receptor-related protein 5/6
K02353  segment polarity protein dishevelled
K03069  frequently rearranged in advanced T-cell lymphomas 1
K03096  frequently rearranged in advanced T-cell lymphomas 2
K03083  glycogen synthase kinase 3 beta [EC:]
K02157  axin 1
K04385  axin 2
K02085  adenomatosis polyposis coli protein
K02105  catenin beta 1
K08957  casein kinase 1, alpha [EC:]
K02620  transcription factor 7
K04490  transcription factor 7-like 1
K04491  transcription factor 7-like 2
K04492  lymphoid enhancer-binding factor 1
K04377  Myc proto-oncogene protein
K04503  G1/S-specific cyclin-D1
K11126  telomerase reverse transcriptase [EC:]
K22183  telomerase RNA component
K04357  epidermal growth factor
K04361  epidermal growth factor receptor [EC:]
K05083  receptor tyrosine-protein kinase erbB-2 [EC:]
K06279  SHC-transforming protein 1
K17447  SHC-transforming protein 2
K17448  SHC-transforming protein 3
K17449  SHC-transforming protein 4
K04364  growth factor receptor-bound protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K08845  A-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:]
K07203  serine/threonine-protein kinase mTOR [EC:]
K04688  ribosomal protein S6 kinase beta [EC:]
K02161  apoptosis regulator Bcl-2
K08734  DNA mismatch repair protein MLH1
K06624  cyclin-dependent kinase inhibitor 1B
K02206  cyclin-dependent kinase 2 [EC:]
K06626  G1/S-specific cyclin-E1
K06618  retinoblastoma-associated protein
K17454  transcription factor E2F1
K09389  transcription factor E2F2
K06620  transcription factor E2F3
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K04674  TGF-beta receptor type-1 [EC:]
K04388  TGF-beta receptor type-2 [EC:]
K04500  mothers against decapentaplegic homolog 2
K23605  mothers against decapentaplegic homolog 3
K04501  mothers against decapentaplegic homolog 4
K04685  cyclin-dependent kinase inhibitor 2B
K05689  cadherin 1, type 1, E-cadherin
K05691  catenin alpha
K10056  junction plakoglobin
K05460  hepatocyte growth factor
K05099  proto-oncogene tyrosine-protein kinase Met [EC:]
K18496  fibroblast growth factor 1
K18497  fibroblast growth factor 2
K04358  fibroblast growth factor
K22603  fibroblast growth factor 19
K22429  fibroblast growth factor 21
K22428  fibroblast growth factor 23
K05093  fibroblast growth factor receptor 2 [EC:]
K09593  GRB2-associated-binding protein 1
C00039  DNA
C00777  Retinoate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C15493  9-cis-Retinoic acid
Tan P, Yeoh KG
Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma.
Gastroenterology 149:1153-1162.e3 (2015)
Riquelme I, Saavedra K, Espinoza JA, Weber H, Garcia P, Nervi B, Garrido M, Corvalan AH, Roa JC, Bizama C
Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy.
Oncotarget 6:24750-79 (2015)
Stock M, Otto F
Gene deregulation in gastric cancer.
Gene 360:1-19 (2005)
Panani AD
Cytogenetic and molecular aspects of gastric cancer: clinical implications.
Cancer Lett 266:99-115 (2008)
Vauhkonen M, Vauhkonen H, Sipponen P
Pathology and molecular biology of gastric cancer.
Best Pract Res Clin Gastroenterol 20:651-74 (2006)
Smith MG, Hold GL, Tahara E, El-Omar EM.
Cellular and molecular aspects of gastric cancer.
World J Gastroenterol 12:2979-90 (2006)
Zheng L, Wang L, Ajani J, Xie K.
Molecular basis of gastric cancer development and progression.
Gastric Cancer 7:61-77 (2004)
Yuasa Y
Control of gut differentiation and intestinal-type gastric carcinogenesis.
Nat Rev Cancer 3:592-600 (2003)
Wessler S, Krisch LM, Elmer DP, Aberger F
From inflammation to gastric cancer - the importance of Hedgehog/GLI signaling in Helicobacter pylori-induced chronic inflammatory and neoplastic diseases.
Cell Commun Signal 15:15 (2017)
Yan LH, Wei WY, Xie YB, Xiao Q
New insights into the functions and localization of the homeotic gene CDX2 in gastric cancer.
World J Gastroenterol 20:3960-6 (2014)
Hayashi K, Yokozaki H, Goodison S, Oue N, Suzuki T, Lotan R, Yasui W, Tahara E
Inactivation of retinoic acid receptor beta by promoter CpG hypermethylation in gastric cancer.
Differentiation 68:13-21 (2001)
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
Distinct Subtypes of Gastric Cancer Defined by Molecular Characterization Include Novel Mutational Signatures with Prognostic Capability.
Cancer Res 76:1724-32 (2016)
Wadhwa R, Song S, Lee JS, Yao Y, Wei Q, Ajani JA
Gastric cancer-molecular and clinical dimensions.
Nat Rev Clin Oncol 10:643-55 (2013)
Bertotti A, Sassi F
Molecular Pathways: Sensitivity and Resistance to Anti-EGFR Antibodies.
Clin Cancer Res 21:3377-83 (2015)
Appleman LJ
MET signaling pathway: a rational target for cancer therapy.
J Clin Oncol 29:4837-8 (2011)
Eder JP, Vande Woude GF, Boerner SA, LoRusso PM
Novel therapeutic inhibitors of the c-Met signaling pathway in cancer.
Clin Cancer Res 15:2207-14 (2009)
Feng Y, Ma PC
Anti-MET targeted therapy has come of age: the first durable complete response with MetMAb in metastatic gastric cancer.
Cancer Discov 1:550-4 (2011)
Katoh M, Nakagama H
FGF receptors: cancer biology and therapeutics.
Med Res Rev 34:280-300 (2014)
Katoh M
FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies.
J Invest Dermatol 129:1861-7 (2009)
Katoh M
Genetic alterations of FGF receptors: an emerging field in clinical cancer diagnostics and therapeutics.
Expert Rev Anticancer Ther 10:1375-9 (2010)
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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