KEGG   PATHWAY: hsa05210Help
Entry
hsa05210                    Pathway                                

Name
Colorectal cancer - Homo sapiens (human)
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
hsa05210

All organismsOrtholog table
Network
N00012  
Mutation-activated KRAS/NRAS to ERK signaling pathway
N00032  
Mutation-activated KRAS/NRAS to PI3K signaling pathway
N00057  
Mutation-inactivated APC to Wnt signaling pathway
N00058  
Mutation-activated CTNNB1 to Wnt signaling pathway
N00064  
Mutation-inactivated TGFBR2 to TGF-beta signaling pathway
N00065  
Mutation-inactivated SMAD2 to TGF-beta signaling pathway
N00099  
Mutation-inactivated BAX to apoptotic pathway
N00102  
Loss of DCC to DCC-apoptotic pathway
N00104  
Mutation-activated KRAS to RalGDS signaling pathway
N00115  
Mutation-inactivated TP53 to transcription
Disease
H00020  
Colorectal cancer
H00857  
Oligodontia-colorectal cancer syndrome
H00876  
Mismatch repair deficiency
H01023  
Juvenile polyposis syndrome
H01025  
Familial adenomatous polyposis
Organism
Homo sapiens (human) [GN:hsa]
Gene
2932  
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
8312  
AXIN1; axin 1 [KO:K02157]
8313  
AXIN2; axin 2 [KO:K04385]
1499  
CTNNB1; catenin beta 1 [KO:K02105]
324  
APC; APC, WNT signaling pathway regulator [KO:K02085]
10297  
APC2; APC2, WNT signaling pathway regulator [KO:K02085]
6932  
TCF7; transcription factor 7 [KO:K02620]
83439  
TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  
TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  
LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
332  
BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
4609  
MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377]
595  
CCND1; cyclin D1 [KO:K04503]
3845  
KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
207  
AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
572  
BAD; BCL2 associated agonist of cell death [KO:K02158]
842  
CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
369  
ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  
BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
3725  
JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
2353  
FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
5900  
RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
5898  
RALA; RAS like proto-oncogene A [KO:K07834]
5899  
RALB; RAS like proto-oncogene B [KO:K07835]
5879  
RAC1; Rac family small GTPase 1 [KO:K04392]
5880  
RAC2; Rac family small GTPase 2 [KO:K07860]
5881  
RAC3; Rac family small GTPase 3 [KO:K07861]
387  
RHOA; ras homolog family member A [KO:K04513]
5599  
MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  
MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  
MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
1630  
DCC; DCC netrin 1 receptor [KO:K06765]
836  
CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
26060  
APPL1; adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 [KO:K08733]
7040  
TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  
TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  
TGFB3; transforming growth factor beta 3 [KO:K13377]
7046  
TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
7048  
TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
4087  
SMAD2; SMAD family member 2 [KO:K04500]
4088  
SMAD3; SMAD family member 3 [KO:K04500]
4089  
SMAD4; SMAD family member 4 [KO:K04501]
4292  
MLH1; mutL homolog 1 [KO:K08734]
4436  
MSH2; mutS homolog 2 [KO:K08735]
4437  
MSH3; mutS homolog 3 [KO:K08736]
2956  
MSH6; mutS homolog 6 [KO:K08737]
581  
BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
5366  
PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
10018  
BCL2L11; BCL2 like 11 [KO:K16341]
27113  
BBC3; BCL2 binding component 3 [KO:K10132]
596  
BCL2; BCL2, apoptosis regulator [KO:K02161]
54205  
CYCS; cytochrome c, somatic [KO:K08738]
7157  
TP53; tumor protein p53 [KO:K04451]
1026  
CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
1647  
GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
4616  
GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
10912  
GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
578  
BAK1; BCL2 antagonist/killer 1 [KO:K14021]
1643  
DDB2; damage specific DNA binding protein 2 [KO:K10140]
51426  
POLK; DNA polymerase kappa [KO:K03511] [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
KO pathway
 

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