KEGG   PATHWAY: mcf05210
Entry
mcf05210                    Pathway                                
Name
Colorectal cancer - Macaca fascicularis (crab-eating macaque)
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
mcf05210  Colorectal cancer
mcf05210

Organism
Macaca fascicularis (crab-eating macaque) [GN:mcf]
Gene
102133756  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102142970  AXIN1; axin-1 isoform X1 [KO:K02157]
102129656  AXIN2; axin-2 isoform X1 [KO:K04385]
102146984  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
102126553  APC; adenomatous polyposis coli protein isoform X2 [KO:K02085]
102123489  APC2; adenomatous polyposis coli protein 2 isoform X3 [KO:K02085]
102142248  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
102125513  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
102116470  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
101925349  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
102120307  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
102133017  baculoviral IAP repeat-containing protein 5-like [KO:K08731]
102127966  MYC; myc proto-oncogene protein [KO:K04377]
102135329  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102131483  KRAS; GTPase KRas isoform X1 [KO:K07827]
102143464  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102142026  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102122725  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102137291  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
101866246  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102124804  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102144461  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102142406  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102132744  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102121921  BAD; bcl2-associated agonist of cell death [KO:K02158]
102126830  CASP9; LOW QUALITY PROTEIN: caspase-9 [KO:K04399] [EC:3.4.22.62]
101925249  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
101866436  BRAF; serine/threonine-protein kinase B-raf isoform X4 [KO:K04365] [EC:2.7.11.1]
102125312  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102141214  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102140855  dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102145011  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102116996  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
102126446  JUN; transcription factor AP-1 [KO:K04448]
102143716  FOS; proto-oncogene c-Fos [KO:K04379]
102121408  RALGDS; ral guanine nucleotide dissociation stimulator isoform X3 [KO:K08732]
102124288  ral-GDS-related protein-like isoform X1 [KO:K08732]
102125458  LOW QUALITY PROTEIN: ral-GDS-related protein-like [KO:K08732]
102124292  RALA; ras-related protein Ral-A [KO:K07834]
101925782  RALB; ras-related protein Ral-B [KO:K07835]
101866593  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
102134837  ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
102137056  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
102143597  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
101865630  RHOA; transforming protein RhoA [KO:K04513]
102118497  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102126339  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102121272  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102138576  DCC; netrin receptor DCC isoform X4 [KO:K06765]
102144182  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
102126071  APPL1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
102129546  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
101925182  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
102119907  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
102115287  TGFBR1; TGF-beta receptor type-1 isoform X3 [KO:K04674] [EC:2.7.11.30]
102134273  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
101925163  SMAD2; mothers against decapentaplegic homolog 2 isoform X5 [KO:K04500]
102146086  SMAD3; mothers against decapentaplegic homolog 3 isoform X2 [KO:K23605]
102142438  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
102132986  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
101867487  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
102136760  MSH3; DNA mismatch repair protein Msh3 isoform X1 [KO:K08736]
102143419  MSH6; DNA mismatch repair protein Msh6 isoform X1 [KO:K08737]
102132255  BAX; apoptosis regulator BAX isoform X6 [KO:K02159]
102120192  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 isoform X2 [KO:K10131]
102135074  BCL2L11; bcl-2-like protein 11 isoform X5 [KO:K16341]
102119825  BBC3; bcl-2-binding component 3 isoform X3 [KO:K10132]
102138212  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
102117102  cytochrome c-like [KO:K08738]
102120205  cytochrome c [KO:K08738]
102125088  cytochrome c-like [KO:K08738]
102136392  cytochrome c-like [KO:K08738]
102127614  cytochrome c-like [KO:K08738]
102141866  cytochrome c-like [KO:K08738]
107127908  cytochrome c-like [KO:K08738]
102120841  cytochrome c-like [KO:K08738]
102123704  cytochrome c-like [KO:K08738]
107130218  cytochrome c-like [KO:K08738]
102135998  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
102136063  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102128083  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102135480  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102115080  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102142357  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102124623  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
101925142  POLK; DNA polymerase kappa isoform X2 [KO:K03511] [EC:2.7.7.7]
102123415  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102145541  TGFA; protransforming growth factor alpha isoform X2 [KO:K08774]
102119238  EREG; proepiregulin [KO:K09784]
102118341  AREG; amphiregulin [KO:K09782]
102138724  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
102118276  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102135079  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102138313  SOS2; son of sevenless homolog 2 [KO:K03099]
102118744  HRAS; GTPase HRas isoform X1 [KO:K02833]
102137913  NRAS; GTPase NRas [KO:K07828]
102128371  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101925564  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X3 [KO:K04688] [EC:2.7.11.1]
102134845  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
mcf04010  MAPK signaling pathway
mcf04012  ErbB signaling pathway
mcf04110  Cell cycle
mcf04115  p53 signaling pathway
mcf04150  mTOR signaling pathway
mcf04151  PI3K-Akt signaling pathway
mcf04210  Apoptosis
mcf04310  Wnt signaling pathway
mcf04350  TGF-beta signaling pathway
KO pathway
ko05210   
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