KEGG   PATHWAY: dsp05210
Entry
dsp05210                    Pathway                                
Name
Colorectal cancer - Dipodomys spectabilis (banner-tailed kangaroo rat)
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
dsp05210  Colorectal cancer
dsp05210

Organism
Dipodomys spectabilis (banner-tailed kangaroo rat) [GN:dsp]
Gene
122096813  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
122098148  Axin1; axin-1 isoform X1 [KO:K02157]
122094958  Axin2; axin-2 [KO:K04385]
122124883  Ctnnb1; catenin beta-1 [KO:K02105]
122122822  Apc2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
122118219  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
122115432  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
122116902  Tcf7l1; transcription factor 7-like 1 [KO:K04490]
122115716  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
122127220  Lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
122096602  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
122097907  baculoviral IAP repeat-containing protein 5 [KO:K08731]
122102408  Myc; myc proto-oncogene protein [KO:K04377]
122099882  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
122098841  Kras; GTPase KRas isoform X1 [KO:K07827]
122095294  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122121501  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122107232  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122123339  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like [KO:K00922] [EC:2.7.1.153]
122108047  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122100872  Pik3r2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122117343  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122097416  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122101263  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122126696  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122105036  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
122099125  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
122098764  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
122105936  Braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
122107826  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122114391  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122099331  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122095844  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122096287  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122108943  Jun; transcription factor AP-1 [KO:K04448]
122118881  Fos; proto-oncogene c-Fos [KO:K04379]
122120732  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120746  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120747  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120774  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120806  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120809  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120812  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120814  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120818  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120862  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120901  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120903  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122120905  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122114492  uncharacterized protein LOC122114492 isoform X1 [KO:K08732]
122114847  LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122124476  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
122109018  Ralgds; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
122120863  Rala; ras-related protein Ral-A [KO:K07834]
122112437  Ralb; ras-related protein Ral-B [KO:K07835]
122113510  Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
122119204  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
122099403  Rac3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
122095683  Rhoa; transforming protein RhoA [KO:K04513]
122115017  transforming protein RhoA-like [KO:K04513]
122097824  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
122115378  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
122116492  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122104345  Dcc; netrin receptor DCC [KO:K06765]
122126104  Casp3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
122108001  Appl1; DCC-interacting protein 13-alpha [KO:K08733]
122097410  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
122109464  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
122118877  Tgfb3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
122121204  Tgfbr1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
122096026  Tgfbr2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
122104270  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
122114693  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
122104309  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
122096100  Mlh1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
122104558  Msh2; DNA mismatch repair protein Msh2 [KO:K08735]
122117188  Msh3; DNA mismatch repair protein Msh3 isoform X1 [KO:K08736]
122104577  Msh6; DNA mismatch repair protein Msh6 [KO:K08737]
122125840  Bax; apoptosis regulator BAX [KO:K02159]
122098053  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
122121284  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
122125754  Bbc3; bcl-2-binding component 3 isoform X1 [KO:K10132]
122119434  Bcl2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
122110854  cytochrome c-like [KO:K08738]
122112201  cytochrome c, somatic [KO:K08738]
122115021  cytochrome c, testis-specific [KO:K08738]
122124195  cytochrome c, somatic-like [KO:K08738]
122116980  cytochrome c, somatic-like [KO:K08738]
122117286  cytochrome c, somatic-like [KO:K08738]
122100440  Tp53; cellular tumor antigen p53 [KO:K04451]
122111380  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
122104319  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122113654  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122099301  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122111128  Bak1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
122104989  Ddb2; DNA damage-binding protein 2 [KO:K10140]
122117376  Polk; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
122127051  Egf; pro-epidermal growth factor [KO:K04357]
122125176  Tgfa; protransforming growth factor alpha [KO:K08774]
122106918  Ereg; proepiregulin [KO:K09784]
122106898  Areg; amphiregulin [KO:K09782]
122112209  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
122128376  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
122104519  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
122106484  Sos2; son of sevenless homolog 2 [KO:K03099]
122095011  Hras; GTPase HRas isoform X1 [KO:K02833]
122118367  Nras; GTPase NRas [KO:K07828]
122121508  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
122105362  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
122117335  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
dsp04010  MAPK signaling pathway
dsp04012  ErbB signaling pathway
dsp04110  Cell cycle
dsp04115  p53 signaling pathway
dsp04150  mTOR signaling pathway
dsp04151  PI3K-Akt signaling pathway
dsp04210  Apoptosis
dsp04310  Wnt signaling pathway
dsp04350  TGF-beta signaling pathway
KO pathway
ko05210   
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