KEGG   PATHWAY: ko05210Help
Entry
ko05210                     Pathway                                

Name
Colorectal cancer
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; Cancers
BRITE hierarchy
Pathway map
Colorectal cancer
ko05210

All organismsOrtholog table
Disease
H00020  
Colorectal cancer
H00857  
Oligodontia-colorectal cancer syndrome
H00876  
Mismatch repair deficiency
H01023  
Juvenile polyposis syndrome
H01025  
Familial adenomatous polyposis
Orthology
K03083  
glycogen synthase kinase 3 beta [EC:2.7.11.26]
K02157  
axin 1
K04385  
axin 2
K02105  
catenin beta 1
K02085  
adenomatosis polyposis coli protein
K02620  
transcription factor 7
K04490  
transcription factor 7-like 1
K04491  
transcription factor 7-like 2
K04492  
lymphoid enhancer-binding factor 1
K08731  
baculoviral IAP repeat-containing protein 5
K04377  
Myc proto-oncogene protein
K04503  
G1/S-specific cyclin-D1
K07827  
GTPase KRas
K00922  
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  
phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  
RAC serine/threonine-protein kinase [EC:2.7.11.1]
K02158  
Bcl-2-antagonist of cell death
K04399  
caspase 9 [EC:3.4.22.62]
K08845  
A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04365  
B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  
RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  
mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  
mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04448  
transcription factor AP-1
K04379  
proto-oncogene protein c-fos
K08732  
ral guanine nucleotide dissociation stimulator
K07834  
Ras-related protein Ral-A
K07835  
Ras-related protein Ral-B
K04392  
Ras-related C3 botulinum toxin substrate 1
K07860  
Ras-related C3 botulinum toxin substrate 2
K07861  
Ras-related C3 botulinum toxin substrate 3
K04513  
Ras homolog gene family, member A
K04440  
c-Jun N-terminal kinase [EC:2.7.11.24]
K06765  
deleted in colorectal carcinoma
K02187  
caspase 3 [EC:3.4.22.56]
K08733  
DCC-interacting protein 13 alpha
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:2.7.11.30]
K04388  
TGF-beta receptor type-2 [EC:2.7.11.30]
K04500  
mothers against decapentaplegic homolog 2/3
K04501  
mothers against decapentaplegic homolog 4
K08734  
DNA mismatch repair protein MLH1
K08735  
DNA mismatch repair protein MSH2
K08736  
DNA mismatch repair protein MSH3
K08737  
DNA mismatch repair protein MSH6
K02159  
apoptosis regulator BAX
K10131  
phorbol-12-myristate-13-acetate-induced protein 1
K16341  
Bcl-2-like protein 11
K10132  
Bcl-2-binding component 3
K02161  
apoptosis regulator Bcl-2
K08738  
cytochrome c
K04451  
tumor protein p53
K06625  
cyclin-dependent kinase inhibitor 1A
K04402  
growth arrest and DNA-damage-inducible protein
K14021  
Bcl-2 homologous antagonist/killer
K10140  
DNA damage-binding protein 2
K03511  
DNA polymerase kappa [EC:2.7.7.7]
Reference
  Authors
Grady WM.
  Title
Genomic instability and colon cancer.
  Journal
Cancer Metastasis Rev 23:11-27 (2004)
DOI:10.1023/A:1025861527711
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Arakawa H.
  Title
Netrin-1 and its receptors in tumorigenesis.
  Journal
Nat Rev Cancer 4:978-87 (2004)
DOI:10.1038/nrc1504
Reference
  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
  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
  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
  Authors
Roman C, Saha D, Beauchamp R.
  Title
TGF-beta and colorectal carcinogenesis.
  Journal
Reference
  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
  Authors
Watson AJ.
  Title
Apoptosis and colorectal cancer.
  Journal
Gut 53:1701-9 (2004)
DOI:10.1136/gut.2004.052704
Reference
  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
  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
  Authors
Karnoub AE, Weinberg RA
  Title
Ras oncogenes: split personalities.
  Journal
Nat Rev Mol Cell Biol 9:517-31 (2008)
DOI:10.1038/nrm2438

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