KEGG   PATHWAY: dle05210
Entry
dle05210                    Pathway                                
Name
Colorectal cancer - Delphinapterus leucas (beluga whale)
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
dle05210  Colorectal cancer
dle05210

Disease
H00020  Colorectal cancer
Organism
Delphinapterus leucas (beluga whale) [GN:dle]
Gene
111163022  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
111163760  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
111164258  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
111164342  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
111164391  MYC; myc proto-oncogene protein [KO:K04377]
111165393  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
111165554  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
111165994  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
111166652  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111167640  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
111167945  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
111168040  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111168108  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111168973  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111169265  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111169438  CTNNB1; catenin beta-1 [KO:K02105]
111169895  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
111170340  HRAS; GTPase HRas isoform X1 [KO:K02833]
111170386  RALB; ras-related protein Ral-B [KO:K07835]
111170519  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
111170922  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
111171490  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
111172300  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
111172911  [KO:K08738]
111173177  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
111173401  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
111173839  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111174031  [KO:K08738]
111174197  [KO:K08738]
111174255  APPL1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
111174398  RHOA; transforming protein RhoA [KO:K04513]
111174575  [KO:K08738]
111174785  MSH6; DNA mismatch repair protein Msh6 isoform X1 [KO:K08737]
111174786  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
111174855  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
111175760  [KO:K02649]
111175871  JUN; transcription factor AP-1 [KO:K04448]
111175930  [KO:K08738]
111176008  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111176232  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
111176238  FOS; proto-oncogene c-Fos [KO:K04379]
111176851  KRAS; GTPase KRas [KO:K07827]
111177083  RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
111177477  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
111177559  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111177653  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
111177745  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111177751  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
111178438  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
111178690  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
111178743  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
111179235  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111179996  NRAS; GTPase NRas [KO:K07828]
111180168  [KO:K06765]
111180199  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
111180211  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
111180252  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
111180276  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
111180543  [KO:K08738]
111180640  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
111180693  BBC3; bcl-2-binding component 3 [KO:K10132]
111180824  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
111180855  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111181886  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
111182181  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111182442  TCF7; transcription factor 7 isoform X1 [KO:K02620]
111182681  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X2 [KO:K07861]
111182765  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
111182833  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
111182912  AXIN2; axin-2 isoform X1 [KO:K04385]
111183632  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111183639  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
111183673  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
111183810  BAD; bcl2-associated agonist of cell death [KO:K02158]
111183968  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
111184488  RALA; ras-related protein Ral-A [KO:K07834]
111184548  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111184789  MSH3; DNA mismatch repair protein Msh3 isoform X2 [KO:K08736]
111185093  AXIN1; axin-1 isoform X1 [KO:K02157]
111185272  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
111185755  TP53; cellular tumor antigen p53 [KO:K04451]
111185984  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111186135  EGF; pro-epidermal growth factor [KO:K04357]
111186216  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
111187099  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
111187262  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
111187265  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
111187462  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
111187609  EREG; proepiregulin [KO:K09784]
111187637  AREG; amphiregulin isoform X1 [KO:K09782]
111188083  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
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
dle04010  MAPK signaling pathway
dle04012  ErbB signaling pathway
dle04110  Cell cycle
dle04115  p53 signaling pathway
dle04150  mTOR signaling pathway
dle04151  PI3K-Akt signaling pathway
dle04210  Apoptosis
dle04310  Wnt signaling pathway
dle04350  TGF-beta signaling pathway
KO pathway
ko05210   

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