KEGG   PATHWAY: cdk05210
Entry
cdk05210                    Pathway                                
Name
Colorectal cancer - Camelus dromedarius (Arabian camel)
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
cdk05210  Colorectal cancer
cdk05210

Organism
Camelus dromedarius (Arabian camel) [GN:cdk]
Gene
105090321  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105098424  AXIN1; axin-1 isoform X1 [KO:K02157]
105085712  AXIN2; axin-2 isoform X1 [KO:K04385]
105084622  CTNNB1; catenin beta-1 [KO:K02105]
105095381  APC; adenomatous polyposis coli protein isoform X4 [KO:K02085]
105104128  APC2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
105090254  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
105104146  TCF7L1; transcription factor 7-like 1 [KO:K04490]
105091689  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
105105289  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
105092156  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
105096445  MYC; myc proto-oncogene protein [KO:K04377]
105104393  CCND1; LOW QUALITY PROTEIN: G1/S-specific cyclin-D1 [KO:K04503]
105100066  KRAS; GTPase KRas isoform X1 [KO:K07827]
105086305  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105107003  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105085928  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105084758  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105101867  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
105092913  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
105099264  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
105104845  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105093393  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105101547  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
105107056  CASP9; LOW QUALITY PROTEIN: caspase-9 [KO:K04399] [EC:3.4.22.62]
105102848  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
105091663  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
105093099  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105093267  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105105302  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
105095214  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105102769  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105092850  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
105086086  FOS; proto-oncogene c-Fos [KO:K04379]
105085184  RALGDS; LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator [KO:K08732]
105088273  RALA; ras-related protein Ral-A [KO:K07834]
105088329  RALB; ras-related protein Ral-B isoform X2 [KO:K07835]
105101582  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
105102215  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
105087723  RHOA; transforming protein RhoA [KO:K04513]
105091591  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
105094659  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105100625  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105103604  DCC; netrin receptor DCC [KO:K06765]
105084433  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105089793  APPL1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
105093367  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
105100091  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
105086078  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
105086891  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
105087202  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
105097587  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
105093274  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
105103392  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
105090699  MLH1; DNA mismatch repair protein Mlh1 isoform X2 [KO:K08734]
105092361  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
105084838  MSH3; DNA mismatch repair protein Msh3 isoform X1 [KO:K08736]
105092358  MSH6; DNA mismatch repair protein Msh6 [KO:K08737]
105102890  BAX; apoptosis regulator BAX [KO:K02159]
105089011  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
105092985  BCL2L11; bcl-2-like protein 11 isoform X6 [KO:K16341]
105104049  BBC3; LOW QUALITY PROTEIN: bcl-2-binding component 3 [KO:K10132]
105088999  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
105098528  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
105095080  cytochrome c [KO:K08738]
105092650  cytochrome c [KO:K08738]
105103011  TP53; cellular tumor antigen p53 [KO:K04451]
105101330  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
105086406  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105103609  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105096626  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
105101376  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105106872  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
105084801  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105089905  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
105088937  TGFA; protransforming growth factor alpha [KO:K08774]
105092123  EREG; proepiregulin [KO:K09784]
105091410  AREG; amphiregulin [KO:K09782]
105105749  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
105104642  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105091467  SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
105103654  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105105427  HRAS; GTPase HRas isoform X1 [KO:K02833]
105089630  NRAS; GTPase NRas [KO:K07828]
105107024  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
105097829  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
105104425  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
cdk04010  MAPK signaling pathway
cdk04012  ErbB signaling pathway
cdk04110  Cell cycle
cdk04115  p53 signaling pathway
cdk04150  mTOR signaling pathway
cdk04151  PI3K-Akt signaling pathway
cdk04210  Apoptosis
cdk04310  Wnt signaling pathway
cdk04350  TGF-beta signaling pathway
KO pathway
ko05210   
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