KEGG   PATHWAY: aml05210
Entry
aml05210                    Pathway                                
Name
Colorectal cancer - Ailuropoda melanoleuca (giant panda)
Description
Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC).
Class
Human Diseases; Cancer: specific types
Pathway map
aml05210  Colorectal cancer
aml05210

Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100479224  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100473018  AXIN1; axin-1 isoform X1 [KO:K02157]
100477069  AXIN2; axin-2 isoform X1 [KO:K04385]
100477834  CTNNB1; catenin beta-1 [KO:K02105]
100472257  APC; adenomatous polyposis coli protein isoform X5 [KO:K02085]
100465768  APC2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
100476528  TCF7; transcription factor 7 isoform X2 [KO:K02620]
100480690  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100467719  TCF7L2; transcription factor 7-like 2 isoform X6 [KO:K04491]
100465982  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100475314  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
100464396  MYC; myc proto-oncogene protein [KO:K04377]
100469787  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
100483919  KRAS; GTPase KRas isoform X1 [KO:K07827]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100473937  BAD; bcl2-associated agonist of cell death [KO:K02158]
100483760  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
100475955  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
100469346  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100483834  JUN; transcription factor AP-1 [KO:K04448]
100474867  FOS; proto-oncogene c-Fos [KO:K04379]
100472281  LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator [KO:K08732]
100484672  RALA; ras-related protein Ral-A [KO:K07834]
100481993  RALB; ras-related protein Ral-B [KO:K07835]
100465648  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100469737  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
100468971  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
100476723  RHOA; transforming protein RhoA [KO:K04513]
100477951  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100482196  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100477600  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
105235553  DCC; netrin receptor DCC isoform X1 [KO:K06765]
100469056  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
100463883  APPL1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
100470703  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
100463584  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
100475861  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
100475698  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
100482939  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
100467069  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100479304  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100465063  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100476536  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
100471735  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
100475866  MSH3; DNA mismatch repair protein Msh3 isoform X1 [KO:K08736]
100471984  MSH6; DNA mismatch repair protein Msh6 isoform X1 [KO:K08737]
100471095  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100474991  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
100477763  BCL2L11; bcl-2-like protein 11 isoform X2 [KO:K16341]
100474559  bcl-2-binding component 3, isoforms 1/2 [KO:K10132]
100484344  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
100472074  cytochrome c [KO:K08738]
105241648  cytochrome c-like [KO:K08738]
100468516  TP53; cellular tumor antigen p53 [KO:K04451]
100484923  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100477654  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
100482871  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100470600  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100472241  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
100479738  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100464732  POLK; DNA polymerase kappa isoform X2 [KO:K03511] [EC:2.7.7.7]
100467733  pro-epidermal growth factor isoform X1 [KO:K04357]
100467724  TGFA; protransforming growth factor alpha isoform X3 [KO:K08774]
100464489  EREG; proepiregulin [KO:K09784]
100466983  AREG; amphiregulin [KO:K09782]
100468916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
100474396  SOS2; son of sevenless homolog 2 isoform X9 [KO:K03099]
100482526  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100473836  HRAS; GTPase HRas isoform X1 [KO:K02833]
100464196  NRAS; GTPase NRas [KO:K07828]
100471122  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100484786  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100464998  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:15000146
  Authors
Grady WM.
  Title
Genomic instability and colon cancer.
  Journal
Cancer Metastasis Rev 23:11-27 (2004)
DOI:10.1023/A:1025861527711
Reference
PMID:16555243
  Authors
Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.
  Title
Microsatellite instability in colorectal cancer.
  Journal
Br J Surg 93:395-406 (2006)
DOI:10.1002/bjs.5328
Reference
PMID:11078609
  Authors
Anwar S, Hall C, White J, Deakin M, Farrell W, Elder JB.
  Title
Hereditary non-polyposis colorectal cancer: an updated review.
  Journal
Eur J Surg Oncol 26:635-45 (2000)
DOI:10.1053/ejso.2000.0974
Reference
PMID:16699851
  Authors
Takayama T, Miyanishi K, Hayashi T, Sato Y, Niitsu Y.
  Title
Colorectal cancer: genetics of development and metastasis.
  Journal
J Gastroenterol 41:185-92 (2006)
DOI:10.1007/s00535-006-1801-6
Reference
PMID:12621137
  Authors
Lynch HT, de la Chapelle A.
  Title
Hereditary colorectal cancer.
  Journal
N Engl J Med 348:919-32 (2003)
DOI:10.1056/NEJMra012242
Reference
PMID:12951588
  Authors
Rajagopalan H, Nowak MA, Vogelstein B, Lengauer C.
  Title
The significance of unstable chromosomes in colorectal cancer.
  Journal
Nat Rev Cancer 3:695-701 (2003)
DOI:10.1038/nrc1165
Reference
PMID:10505543
  Authors
Behrens J.
  Title
Cadherins and catenins: role in signal transduction and tumor progression.
  Journal
Cancer Metastasis Rev 18:15-30 (1999)
DOI:10.1023/A:1006200102166
Reference
PMID:16042571
  Authors
Behrens J.
  Title
The role of the Wnt signalling pathway in colorectal tumorigenesis.
  Journal
Biochem Soc Trans 33:672-5 (2005)
DOI:10.1042/BST0330672
Reference
PMID:15349822
  Authors
Behrens J, Lustig B.
  Title
The Wnt connection to tumorigenesis.
  Journal
Int J Dev Biol 48:477-87 (2004)
DOI:10.1387/ijdb.041815jb
Reference
PMID:9196022
  Authors
Polakis P.
  Title
The adenomatous polyposis coli (APC) tumor suppressor.
  Journal
Biochim Biophys Acta 1332:F127-47 (1997)
DOI:10.1016/S0304-419X(97)00008-5
Reference
PMID:12737309
  Authors
Janssen KP.
  Title
Murine models of colorectal cancer: studying the role of oncogenic K-ras.
  Journal
Cell Mol Life Sci 60:495-506 (2003)
DOI:10.1007/s000180300041
Reference
PMID:11459867
  Authors
Adjei AA.
  Title
Blocking oncogenic Ras signaling for cancer therapy.
  Journal
J Natl Cancer Inst 93:1062-74 (2001)
DOI:10.1093/jnci/93.14.1062
Reference
PMID:15573119
  Authors
Arakawa H.
  Title
Netrin-1 and its receptors in tumorigenesis.
  Journal
Nat Rev Cancer 4:978-87 (2004)
DOI:10.1038/nrc1504
Reference
PMID:15310786
  Authors
Mehlen P, Fearon ER.
  Title
Role of the dependence receptor DCC in colorectal cancer pathogenesis.
  Journal
J Clin Oncol 22:3420-8 (2004)
DOI:10.1200/JCO.2004.02.019
Reference
PMID:11223406
  Authors
Peltomaki P.
  Title
DNA mismatch repair and cancer.
  Journal
Mutat Res 488:77-85 (2001)
DOI:10.1016/S1383-5742(00)00058-2
Reference
PMID:15711891
  Authors
Li F, Cao Y, Townsend CM Jr, Ko TC.
  Title
TGF-beta signaling in colon cancer cells.
  Journal
World J Surg 29:306-11 (2005)
DOI:10.1007/s00268-004-7813-6
Reference
PMID:11170304
  Authors
Roman C, Saha D, Beauchamp R.
  Title
TGF-beta and colorectal carcinogenesis.
  Journal
Microsc Res Tech 52:450-7 (2001)
DOI:10.1002/1097-0029(20010215)52:4<450::AID-JEMT1030>3.0.CO;2-O
Reference
PMID:16326109
  Authors
Watson AJ.
  Title
An overview of apoptosis and the prevention of colorectal cancer.
  Journal
Crit Rev Oncol Hematol 57:107-21 (2006)
DOI:10.1016/j.critrevonc.2005.06.005
Reference
PMID:15479695
  Authors
Watson AJ.
  Title
Apoptosis and colorectal cancer.
  Journal
Gut 53:1701-9 (2004)
DOI:10.1136/gut.2004.052704
Reference
PMID:11477132
  Authors
Houlston RS.
  Title
What we could do now: molecular pathology of colorectal cancer.
  Journal
Mol Pathol 54:206-14 (2001)
DOI:10.1136/mp.54.4.206
Reference
PMID:19167459
  Authors
Hector S, Prehn JH
  Title
Apoptosis signaling proteins as prognostic biomarkers in colorectal cancer: a review.
  Journal
Biochim Biophys Acta 1795:117-29 (2009)
DOI:10.1016/j.bbcan.2008.12.002
Reference
PMID:18568040
  Authors
Karnoub AE, Weinberg RA
  Title
Ras oncogenes: split personalities.
  Journal
Nat Rev Mol Cell Biol 9:517-31 (2008)
DOI:10.1038/nrm2438
Reference
PMID:24213116
  Authors
Wang D, Xia D, Dubois RN
  Title
The Crosstalk of PTGS2 and EGF Signaling Pathways in Colorectal Cancer.
  Journal
Cancers (Basel) 3:3894-908 (2011)
DOI:10.3390/cancers3043894
Reference
PMID:20554751
  Authors
Dasari A, Messersmith WA
  Title
New strategies in colorectal cancer: biomarkers of response to epidermal growth factor receptor monoclonal antibodies and potential therapeutic targets in phosphoinositide 3-kinase and mitogen-activated protein kinase pathways.
  Journal
Clin Cancer Res 16:3811-8 (2010)
DOI:10.1158/1078-0432.CCR-09-2283
Reference
PMID:26149458
  Authors
Hutchinson RA, Adams RA, McArt DG, Salto-Tellez M, Jasani B, Hamilton PW
  Title
Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer.
  Journal
J Transl Med 13:217 (2015)
DOI:10.1186/s12967-015-0531-z
Related
pathway
aml04010  MAPK signaling pathway
aml04012  ErbB signaling pathway
aml04110  Cell cycle
aml04115  p53 signaling pathway
aml04150  mTOR signaling pathway
aml04151  PI3K-Akt signaling pathway
aml04210  Apoptosis
aml04310  Wnt signaling pathway
aml04350  TGF-beta signaling pathway
KO pathway
ko05210   
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