KEGG   PATHWAY: dord05210
Entry
dord05210                   Pathway                                
Name
Colorectal cancer - Dipodomys ordii (Ord's 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
dord05210  Colorectal cancer
dord05210

Organism
Dipodomys ordii (Ord's kangaroo rat) [GN:dord]
Gene
105987982  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105982203  Axin1; axin-1 [KO:K02157]
106000715  Axin2; axin-2 [KO:K04385]
105990328  Apc2; adenomatous polyposis coli protein 2 [KO:K02085]
105988701  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
105996789  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
106000204  Tcf7l1; transcription factor 7-like 1 [KO:K04490]
105986725  Tcf7l2; transcription factor 7-like 2 [KO:K04491]
105991153  Lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
106003260  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
105992358  Myc; myc proto-oncogene protein [KO:K04377]
105989065  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
105992272  Kras; GTPase KRas isoform X1 [KO:K07827]
105999080  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105999614  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
106000559  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
106001473  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105985370  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105986178  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105986533  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105983045  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105998099  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105989249  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
105989961  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
106000303  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
105989470  Braf; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
105981244  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
105981136  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105990471  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105981830  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105997225  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105986734  Fos; proto-oncogene c-Fos [KO:K04379]
105987223  LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator-like [KO:K08732]
105993771  LOW QUALITY PROTEIN: ral guanine nucleotide dissociation stimulator-like [KO:K08732]
105989429  Ralgds; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
105998338  Rala; ras-related protein Ral-A [KO:K07834]
105988915  Ralb; ras-related protein Ral-B [KO:K07835]
105990882  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
105992088  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
105998414  Rac3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
105994567  Rhoa; transforming protein RhoA [KO:K04513]
105996777  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105988509  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105998906  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105987617  Dcc; netrin receptor DCC [KO:K06765]
105992928  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105996564  Appl1; DCC-interacting protein 13-alpha [KO:K08733]
106000874  Tgfb1; transforming growth factor beta-1 [KO:K13375]
105984796  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105983993  Tgfb3; transforming growth factor beta-3 isoform X1 [KO:K13377]
105990763  Tgfbr1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
105994860  Tgfbr2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
105987654  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
105981178  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
105987581  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
105993750  Mlh1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
105986810  Msh2; DNA mismatch repair protein Msh2 [KO:K08735]
105985316  Msh3; DNA mismatch repair protein Msh3 [KO:K08736]
105986844  Msh6; DNA mismatch repair protein Msh6 [KO:K08737]
105994373  Bax; apoptosis regulator BAX [KO:K02159]
105988277  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
105987599  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
105991774  cytochrome c, somatic [KO:K08738]
105994518  cytochrome c, testis-specific [KO:K08738]
105983546  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105995758  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105990235  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105988868  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
106001326  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105999887  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
105996079  Ddb2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
105992438  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105991200  Egf; pro-epidermal growth factor [KO:K04357]
105990143  Tgfa; protransforming growth factor alpha [KO:K08774]
105988547  Ereg; proepiregulin [KO:K09784]
105988546  Areg; amphiregulin [KO:K09782]
106000675  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
106003155  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
105986795  Sos1; son of sevenless homolog 1 [KO:K03099]
105982575  Sos2; son of sevenless homolog 2 [KO:K03099]
105998617  Hras; GTPase HRas isoform X1 [KO:K02833]
105991947  Nras; GTPase NRas [KO:K07828]
105997410  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105983479  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
105989224  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
106001479  ribosomal protein S6 kinase beta-1 [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
dord04010  MAPK signaling pathway
dord04012  ErbB signaling pathway
dord04110  Cell cycle
dord04115  p53 signaling pathway
dord04150  mTOR signaling pathway
dord04151  PI3K-Akt signaling pathway
dord04210  Apoptosis
dord04310  Wnt signaling pathway
dord04350  TGF-beta signaling pathway
KO pathway
ko05210   
LinkDB

DBGET integrated database retrieval system