KEGG   PATHWAY: uah05210
Entry
uah05210                    Pathway                                
Name
Colorectal cancer - Ursus arctos horribilis (North American brown bear)
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
uah05210  Colorectal cancer
uah05210

Organism
Ursus arctos horribilis (North American brown bear) [GN:uah]
Gene
113251972  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
113245367  AXIN1; axin-1 isoform X1 [KO:K02157]
113265246  AXIN2; axin-2 [KO:K04385]
113253816  CTNNB1; catenin beta-1 [KO:K02105]
113254991  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
113242735  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
113261735  TCF7; transcription factor 7 isoform X1 [KO:K02620]
113243231  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
113251942  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
113255544  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
113244569  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
113252726  MYC; myc proto-oncogene protein [KO:K04377]
113243982  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
113257792  KRAS; GTPase KRas isoform X1 [KO:K07827]
113254799  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
113270537  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113253989  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113256705  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
113254730  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
113255266  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113267192  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
113243572  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113262966  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113244178  BAD; bcl2-associated agonist of cell death [KO:K02158]
113270476  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
113265980  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
113265167  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
113257190  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
113240885  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
113242822  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
113267646  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
113247020  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
113254611  JUN; transcription factor AP-1 [KO:K04448]
113270317  FOS; proto-oncogene c-Fos [KO:K04379]
113266555  RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
113249103  ral guanine nucleotide dissociation stimulator-like isoform X1 [KO:K08732]
113249140  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
113247941  ral guanine nucleotide dissociation stimulator-like isoform X1 [KO:K08732]
113250009  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
113258228  RALA; ras-related protein Ral-A isoform X1 [KO:K07834]
113263462  RALB; ras-related protein Ral-B [KO:K07835]
113267943  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
113241811  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
113244670  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
113256876  RHOA; transforming protein RhoA [KO:K04513]
113263180  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
113261548  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
113243106  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
113253561  DCC; netrin receptor DCC [KO:K06765]
113262259  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
113257000  APPL1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
113243540  TGFB1; transforming growth factor beta-1 isoform X1 [KO:K13375]
113268733  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
113270312  TGFB3; transforming growth factor beta-3 [KO:K13377]
113260405  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
113253847  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
113253394  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
113240893  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
113253422  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
113253768  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
113245944  MSH2; DNA mismatch repair protein Msh2 isoform X1 [KO:K08735]
113255156  MSH3; DNA mismatch repair protein Msh3 isoform X1 [KO:K08736]
113245929  MSH6; DNA mismatch repair protein Msh6 [KO:K08737]
113243322  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
113253468  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
113242278  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
113243380  BBC3; bcl-2-binding component 3 [KO:K10132]
113253490  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
113248234  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
113261698  cytochrome c [KO:K08738]
113271152  TP53; cellular tumor antigen p53 [KO:K04451]
113243864  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
113254548  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
113270128  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
113242768  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
113243812  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
113264969  DDB2; DNA damage-binding protein 2 [KO:K10140]
113255198  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
113255562  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
113268295  TGFA; protransforming growth factor alpha [KO:K08774]
113263086  EREG; proepiregulin [KO:K09784]
113263049  AREG; amphiregulin [KO:K09782]
113257444  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
113244637  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
113266205  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
113241630  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
113257418  GTPase HRas-like [KO:K02833]
113244394  NRAS; GTPase NRas [KO:K07828]
113270510  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
113244028  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
113268897  RPS6KB1; ribosomal protein S6 kinase beta-1 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
uah04010  MAPK signaling pathway
uah04012  ErbB signaling pathway
uah04110  Cell cycle
uah04115  p53 signaling pathway
uah04150  mTOR signaling pathway
uah04151  PI3K-Akt signaling pathway
uah04210  Apoptosis
uah04310  Wnt signaling pathway
uah04350  TGF-beta signaling pathway
KO pathway
ko05210   
LinkDB

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