KEGG   PATHWAY: ccan05210
Entry
ccan05210                   Pathway                                
Name
Colorectal cancer - Castor canadensis (American beaver)
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
ccan05210  Colorectal cancer
ccan05210

Organism
Castor canadensis (American beaver) [GN:ccan]
Gene
109685333  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
109694685  Axin1; axin-1 isoform X1 [KO:K02157]
109681311  Axin2; axin-2 [KO:K04385]
109689873  Ctnnb1; catenin beta-1 [KO:K02105]
109691007  Apc2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
109699342  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
109689465  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
109686184  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
109688561  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
109688935  lymphoid enhancer-binding factor 1 [KO:K04492]
109683144  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
109699943  Myc; myc proto-oncogene protein [KO:K04377]
109696351  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
109687060  Kras; GTPase KRas [KO:K07827]
109681900  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109689664  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109682432  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109694666  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
109682554  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109688536  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109691810  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109686235  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109683261  Bad; bcl2-associated agonist of cell death [KO:K02158]
109692548  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
109696670  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
109682021  serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
109698982  LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf-like [KO:K04365] [EC:2.7.11.1]
109694940  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109687824  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109687808  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
109683259  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109684381  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
109700777  Jun; transcription factor AP-1 [KO:K04448]
109694000  Fos; proto-oncogene c-Fos [KO:K04379]
109677869  LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator-like [KO:K08732]
109677013  LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator-like [KO:K08732]
109678448  LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator-like [KO:K08732]
109683009  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
109690895  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
109690997  Ralgds; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
109701840  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
109701306  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
109699717  LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator-like [KO:K08732]
109701457  Rala; ras-related protein Ral-A [KO:K07834]
109699956  Ralb; ras-related protein Ral-B [KO:K07835]
109692922  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
109698248  Rac2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
109702872  Rac3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
109697844  Rhoa; transforming protein RhoA [KO:K04513]
109690388  transforming protein RhoA-like isoform X1 [KO:K04513]
109686728  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
109686738  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109703004  mitogen-activated protein kinase 10-like [KO:K04440] [EC:2.7.11.24]
109677269  Dcc; netrin receptor DCC [KO:K06765]
109678444  caspase-3 [KO:K02187] [EC:3.4.22.56]
109678454  caspase-3-like [KO:K02187] [EC:3.4.22.56]
109681666  DCC-interacting protein 13-alpha-like [KO:K08733]
109681669  DCC-interacting protein 13-alpha [KO:K08733]
109685632  Tgfb1; transforming growth factor beta-1 [KO:K13375]
109698650  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
109686152  Tgfb3; transforming growth factor beta-3 [KO:K13377]
109691424  Tgfbr1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
109681522  Tgfbr2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
109700302  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 2-like [KO:K04500]
109701514  Smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
109687032  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
109689885  Mlh1; DNA mismatch repair protein Mlh1 [KO:K08734]
109691600  Msh2; LOW QUALITY PROTEIN: DNA mismatch repair protein Msh2 [KO:K08735]
109688113  Msh3; DNA mismatch repair protein Msh3 [KO:K08736]
109691597  Msh6; DNA mismatch repair protein Msh6 [KO:K08737]
109682703  Bax; apoptosis regulator BAX [KO:K02159]
109701119  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
109699272  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
109697533  Bbc3; bcl-2-binding component 3 isoform X1 [KO:K10132]
109693757  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
109679656  cytochrome c-like [KO:K08738]
109697493  cytochrome c, somatic [KO:K08738]
109690717  cytochrome c-like [KO:K08738]
109674834  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
109696503  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
109691045  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109696612  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
109698312  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109686692  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
109696190  Ddb2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
109699936  LOW QUALITY PROTEIN: DNA polymerase kappa-like [KO:K03511] [EC:2.7.7.7]
109700925  Egf; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
109701504  Tgfa; protransforming growth factor alpha [KO:K08774]
109681117  Ereg; proepiregulin [KO:K09784]
109681114  Areg; amphiregulin [KO:K09782]
109693753  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
109681589  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
109685242  Sos1; son of sevenless homolog 1 [KO:K03099]
109686538  son of sevenless homolog 2 [KO:K03099]
109698042  Hras; GTPase HRas isoform X1 [KO:K02833]
109696062  Nras; GTPase NRas [KO:K07828]
109689656  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
109688624  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
109685124  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
ccan04010  MAPK signaling pathway
ccan04012  ErbB signaling pathway
ccan04110  Cell cycle
ccan04115  p53 signaling pathway
ccan04150  mTOR signaling pathway
ccan04151  PI3K-Akt signaling pathway
ccan04210  Apoptosis
ccan04310  Wnt signaling pathway
ccan04350  TGF-beta signaling pathway
KO pathway
ko05210   
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