KEGG   PATHWAY: mpah05210
Entry
mpah05210                   Pathway                                
Name
Colorectal cancer - Mus pahari (shrew mouse)
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
mpah05210  Colorectal cancer
mpah05210

Organism
Mus pahari (shrew mouse) [GN:mpah]
Gene
110329614  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
110338127  Axin1; axin-1 isoform X1 [KO:K02157]
110331423  Axin2; axin-2 [KO:K04385]
110328516  Ctnnb1; catenin beta-1 isoform X1 [KO:K02105]
110333195  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
110326173  Apc2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
110332085  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
110315696  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
110313411  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
110319903  Lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
110332414  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
110334656  Myc; myc proto-oncogene protein [KO:K04377]
110322378  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
110316221  Kras; GTPase KRas isoform X1 [KO:K07827]
110323448  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110319750  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110327251  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110328811  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110336420  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110322865  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110317258  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110324386  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110322284  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110326250  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110323338  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
110314283  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
110316269  Braf; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
110314893  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110327244  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110326321  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110329343  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110320020  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
110323252  Jun; transcription factor AP-1 [KO:K04448]
110324365  Fos; proto-oncogene c-Fos isoform X1 [KO:K04379]
110317707  Ralgds; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
110333717  Rala; ras-related protein Ral-A [KO:K07834]
110321584  Ralb; ras-related protein Ral-B [KO:K07835]
110339030  Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
110334678  Rac2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
110331528  Rac3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
110326378  transforming protein RhoA-like isoform X1 [KO:K04513]
110327907  Rhoa; transforming protein RhoA isoform X1 [KO:K04513]
110330449  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110332652  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110325466  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110333548  Dcc; netrin receptor DCC [KO:K06765]
110336608  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
110325445  Appl1; DCC-interacting protein 13-alpha [KO:K08733]
110336543  Tgfb1; transforming growth factor beta-1 isoform X1 [KO:K13375]
110321649  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
110324521  Tgfb3; transforming growth factor beta-3 [KO:K13377]
110322784  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
110327573  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
110332834  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
110327577  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
110333204  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
110327431  Mlh1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
110335350  Msh2; DNA mismatch repair protein Msh2 [KO:K08735]
110328815  Msh3; DNA mismatch repair protein Msh3 isoform X1 [KO:K08736]
110335576  Msh6; DNA mismatch repair protein Msh6 isoform X1 [KO:K08737]
110320030  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
110333558  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
110318278  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
110336584  Bbc3; bcl-2-binding component 3 [KO:K10132]
110321591  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110332378  cytochrome c-like [KO:K08738]
110316223  cytochrome c, somatic [KO:K08738]
110317786  cytochrome c, testis-specific [KO:K08738]
110331731  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110338236  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
110316550  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
110326839  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110333844  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110338169  Bak1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
110319597  Ddb2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
110329143  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
110320006  Egf; pro-epidermal growth factor isoform X1 [KO:K04357]
110316577  Tgfa; protransforming growth factor alpha [KO:K08774]
110331017  Ereg; proepiregulin [KO:K09784]
110330966  Areg; amphiregulin [KO:K09782]
110330480  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
110331195  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
110335780  Sos1; son of sevenless homolog 1 [KO:K03099]
110324314  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110318967  GTPase HRas-like isoform X1 [KO:K02833]
110319567  Hras; GTPase HRas [KO:K02833]
110338480  GTPase HRas-like [KO:K02833]
110333346  GTPase HRas-like [KO:K02833]
110320340  Nras; GTPase NRas [KO:K07828]
110323363  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110315992  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
110331448  Rps6kb1; ribosomal protein S6 kinase beta-1 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
mpah04010  MAPK signaling pathway
mpah04012  ErbB signaling pathway
mpah04110  Cell cycle
mpah04115  p53 signaling pathway
mpah04150  mTOR signaling pathway
mpah04151  PI3K-Akt signaling pathway
mpah04210  Apoptosis
mpah04310  Wnt signaling pathway
mpah04350  TGF-beta signaling pathway
KO pathway
ko05210   
LinkDB

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