KEGG   PATHWAY: dro05210
Entry
dro05210                    Pathway                                
Name
Colorectal cancer - Desmodus rotundus (common vampire bat)
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
dro05210  Colorectal cancer
dro05210

Organism
Desmodus rotundus (common vampire bat) [GN:dro]
Gene
112320540  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
112298256  AXIN1; axin-1 isoform X1 [KO:K02157]
112316324  AXIN2; axin-2 isoform X1 [KO:K04385]
112309496  CTNNB1; catenin beta-1 [KO:K02105]
112312489  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
112307214  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
112318180  TCF7; transcription factor 7 isoform X1 [KO:K02620]
112302951  TCF7L1; transcription factor 7-like 1 [KO:K04490]
112300313  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
112321441  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
112302993  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 5-like [KO:K08731]
112298801  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
112315592  MYC; myc proto-oncogene protein [KO:K04377]
112317273  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
112318275  KRAS; LOW QUALITY PROTEIN: GTPase KRas [KO:K07827]
112304041  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
112310002  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
112299448  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112307667  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112321016  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112305224  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112314466  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
112311458  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112318919  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112320130  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112317275  BAD; bcl2-associated agonist of cell death [KO:K02158]
112299456  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
112322484  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
112299790  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
112301126  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112311345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112312483  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
112304801  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112301746  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112314642  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
112311412  FOS; proto-oncogene c-Fos [KO:K04379]
112306313  RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
112302767  RALA; ras-related protein Ral-A [KO:K07834]
112313137  RALB; ras-related protein Ral-B [KO:K07835]
112319549  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
112321719  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
112298813  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
112309492  RHOA; transforming protein RhoA [KO:K04513]
112307557  transforming protein RhoA-like isoform X1 [KO:K04513]
112296379  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
112305558  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
112317841  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
112322778  DCC; netrin receptor DCC [KO:K06765]
112306749  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
112301169  APPL1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
112320009  TGFB1; transforming growth factor beta-1 [KO:K13375]
112318906  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
112311221  TGFB3; transforming growth factor beta-3 [KO:K13377]
112304528  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
112309970  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
112322688  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
112322994  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
112309941  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
112297937  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
112307501  MSH3; DNA mismatch repair protein Msh3 [KO:K08736]
112297935  MSH6; DNA mismatch repair protein Msh6 [KO:K08737]
112310132  BAX; apoptosis regulator BAX [KO:K02159]
112319403  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
112312833  BBC3; bcl-2-binding component 3 [KO:K10132]
112322759  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
112306993  cytochrome c [KO:K08738]
112320658  cytochrome c-like [KO:K08738]
112322221  cytochrome c-like [KO:K08738]
112308825  TP53; cellular tumor antigen p53 [KO:K04451]
112302262  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
112312410  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
112307265  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112312272  growth arrest and DNA damage-inducible protein GADD45 beta-like [KO:K04402]
112309280  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112302219  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
112303349  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
112307522  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
112296254  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
112303034  TGFA; protransforming growth factor alpha [KO:K08774]
112320476  AREG; amphiregulin [KO:K09782]
112306912  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
112298645  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
112297971  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
112310995  SOS2; son of sevenless homolog 2 [KO:K03099]
112317099  HRAS; GTPase HRas isoform X1 [KO:K02833]
112313707  NRAS; GTPase NRas [KO:K07828]
112299108  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
112316527  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
112317229  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
dro04010  MAPK signaling pathway
dro04012  ErbB signaling pathway
dro04110  Cell cycle
dro04115  p53 signaling pathway
dro04150  mTOR signaling pathway
dro04151  PI3K-Akt signaling pathway
dro04210  Apoptosis
dro04310  Wnt signaling pathway
dro04350  TGF-beta signaling pathway
KO pathway
ko05210   
LinkDB

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