KEGG   PATHWAY: mleu05210
Entry
mleu05210                   Pathway                                
Name
Colorectal cancer - Mandrillus leucophaeus (drill)
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
mleu05210  Colorectal cancer
mleu05210

Organism
Mandrillus leucophaeus (drill) [GN:mleu]
Gene
105544615  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105529686  AXIN1; axin-1 [KO:K02157]
105548236  AXIN2; axin-2 [KO:K04385]
105542652  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
105551991  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
105529034  APC; adenomatous polyposis coli protein [KO:K02085]
105531321  TCF7; transcription factor 7 isoform X1 [KO:K02620]
105528862  TCF7L1; transcription factor 7-like 1 [KO:K04490]
105530146  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
105546575  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
105545796  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
105537660  baculoviral IAP repeat-containing protein 5-like isoform X1 [KO:K08731]
105537628  MYC; myc proto-oncogene protein [KO:K04377]
105544506  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
105550009  KRAS; GTPase KRas [KO:K07827]
105539923  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105552763  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105549588  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105547376  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105543389  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105531763  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105540494  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105541755  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105542359  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105549098  BAD; bcl2-associated agonist of cell death [KO:K02158]
105549432  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
105541693  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
105550515  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
105542175  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105530797  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105530027  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105541405  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105544764  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105534921  JUN; transcription factor AP-1 [KO:K04448]
105540805  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
105546073  RGL4; ral-GDS-related protein [KO:K08732]
105552366  LOW QUALITY PROTEIN: ral-GDS-related protein-like [KO:K08732]
105533469  LOW QUALITY PROTEIN: ral-GDS-related protein-like [KO:K08732]
105542946  RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
105530438  ral-GDS-related protein-like [KO:K08732]
105537592  ral-GDS-related protein-like [KO:K08732]
105534009  RALA; ras-related protein Ral-A [KO:K07834]
105542066  RALB; ras-related protein Ral-B isoform X1 [KO:K07835]
105551438  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
105546567  ras-related protein Rac1-like [KO:K04392]
105538902  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
105531520  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
105540348  RHOA; transforming protein RhoA [KO:K04513]
105547365  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
105554734  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105537274  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105534661  netrin receptor DCC [KO:K06765]
105552669  caspase-3-like [KO:K02187] [EC:3.4.22.56]
105553959  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105552676  APPL1; DCC-interacting protein 13-alpha [KO:K08733]
105542552  TGFB1; transforming growth factor beta-1 [KO:K13375]
105544786  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105540815  TGFB3; transforming growth factor beta-3 [KO:K13377]
105549297  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
105543507  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
105531149  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
105530839  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
105531177  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
105541060  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
105540850  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
105550607  MSH3; DNA mismatch repair protein Msh3 [KO:K08736]
105540838  MSH6; DNA mismatch repair protein Msh6 isoform X1 [KO:K08737]
105539167  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
105553919  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
105540034  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
105531978  BBC3; bcl-2-binding component 3 [KO:K10132]
105535165  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
105533249  cytochrome c-like [KO:K08738]
105553485  cytochrome c [KO:K08738]
105553918  cytochrome c-like [KO:K08738]
105549520  cytochrome c-like [KO:K08738]
105549866  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105544234  CDKN1A; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1 [KO:K06625]
105551969  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta isoform X1 [KO:K04402]
105535934  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105550104  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
105544178  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105554817  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
105551317  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
105532399  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
105529939  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
105529095  EREG; proepiregulin [KO:K09784]
105529096  AREG; amphiregulin [KO:K09782]
105529594  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
105538707  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105551898  SOS1; son of sevenless homolog 1 [KO:K03099]
105553627  SOS2; son of sevenless homolog 2 [KO:K03099]
105549333  HRAS; GTPase HRas isoform X1 [KO:K02833]
105554356  NRAS; GTPase NRas isoform X1 [KO:K07828]
105551388  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105539063  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
105544470  RPS6KB2; ribosomal protein S6 kinase beta-2 [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
mleu04010  MAPK signaling pathway
mleu04012  ErbB signaling pathway
mleu04110  Cell cycle
mleu04115  p53 signaling pathway
mleu04150  mTOR signaling pathway
mleu04151  PI3K-Akt signaling pathway
mleu04210  Apoptosis
mleu04310  Wnt signaling pathway
mleu04350  TGF-beta signaling pathway
KO pathway
ko05210   
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