KEGG   PATHWAY: epz05210
Entry
epz05210                    Pathway                                
Name
Colorectal cancer - Equus przewalskii (Przewalski's horse)
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
epz05210  Colorectal cancer
epz05210

Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103547424  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103564115  AXIN1; axin 1 [KO:K02157]
103553492  AXIN2; axin 2 [KO:K04385]
103552888  CTNNB1; catenin beta 1 [KO:K02105]
103561228  APC; APC, WNT signaling pathway regulator [KO:K02085]
103543120  TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
103548276  TCF7L1; transcription factor 7 like 1 [KO:K04490]
103564289  TCF7L2; transcription factor 7 like 2 [KO:K04491]
103557035  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
103554048  BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
103567860  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
103546629  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103549076  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103554655  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform-like [KO:K00922] [EC:2.7.1.153]
103552150  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103548220  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103551868  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103561550  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103560497  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103540249  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103555421  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103542187  BAD; BCL2 associated agonist of cell death [KO:K02158]
103565016  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
103555338  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103554541  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103549630  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103543290  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
103547261  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103562408  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103548618  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
103553681  RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
103544618  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
103563476  RALA; RAS like proto-oncogene A [KO:K07834]
103565218  RALB; RAS like proto-oncogene B [KO:K07835]
103552260  ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
103564464  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
103551104  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
103553409  RHOA; ras homolog family member A [KO:K04513]
103549414  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103553980  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103567629  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103554287  DCC; DCC netrin 1 receptor [KO:K06765]
103549132  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
103547870  APPL1; adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 [KO:K08733]
103562543  TGFB1; transforming growth factor beta 1 [KO:K13375]
103543045  TGFB2; transforming growth factor beta 2 [KO:K13376]
103555506  TGFB3; transforming growth factor beta 3 [KO:K13377]
103555266  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
103567708  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
103548562  SMAD2; SMAD family member 2 [KO:K04500]
103549637  SMAD3; SMAD family member 3 [KO:K23605]
103558026  SMAD4; SMAD family member 4 [KO:K04501]
103556094  MLH1; mutL homolog 1 [KO:K08734]
103558101  MSH2; mutS homolog 2 [KO:K08735]
103549605  MSH3; mutS homolog 3 [KO:K08736]
103558461  MSH6; mutS homolog 6 [KO:K08737]
103553312  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
103563750  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
103552644  BCL2L11; BCL2 like 11 [KO:K16341]
103560717  BBC3; BCL2 binding component 3 [KO:K10132]
103550767  BCL2; BCL2, apoptosis regulator [KO:K02161]
103547975  cytochrome c, testis-specific [KO:K08738]
103561978  cytochrome c [KO:K08738]
103557703  TP53; tumor protein p53 [KO:K04451]
103564535  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
103552106  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
103543986  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
103564848  growth arrest and DNA damage-inducible protein GADD45 alpha-like [KO:K04402]
103544222  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
103566732  DDB2; damage specific DNA binding protein 2 [KO:K10140]
103563108  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
103543333  pro-epidermal growth factor-like [KO:K04357]
103547583  TGFA; transforming growth factor alpha [KO:K08774]
103543652  EREG; epiregulin [KO:K09784]
103562708  AREG; amphiregulin [KO:K09782]
103560128  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103546580  GRB2; growth factor receptor bound protein 2 [KO:K04364]
103553088  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103556123  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103567332  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103552675  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103552237  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103565282  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
103559935  RPS6KB2; ribosomal protein S6 kinase B2 [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
epz04010  MAPK signaling pathway
epz04012  ErbB signaling pathway
epz04110  Cell cycle
epz04115  p53 signaling pathway
epz04150  mTOR signaling pathway
epz04151  PI3K-Akt signaling pathway
epz04210  Apoptosis
epz04310  Wnt signaling pathway
epz04350  TGF-beta signaling pathway
KO pathway
ko05210   
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