KEGG   PATHWAY: mun05210
Entry
mun05210                    Pathway                                
Name
Colorectal cancer - Meriones unguiculatus (Mongolian gerbil)
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
mun05210  Colorectal cancer
mun05210

Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110555390  Gsk3b; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
110548696  Axin1; axin-1 isoform X1 [KO:K02157]
110563522  Axin2; axin-2 [KO:K04385]
110561755  Ctnnb1; catenin beta-1 [KO:K02105]
110551354  Apc2; adenomatous polyposis coli protein 2 isoform X2 [KO:K02085]
110551111  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
110549622  Tcf7; transcription factor 7 isoform X6 [KO:K02620]
110541202  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
110545126  Tcf7l2; transcription factor 7-like 2 isoform X10 [KO:K04491]
110553391  Lef1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
110550569  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
110560064  Myc; myc proto-oncogene protein [KO:K04377]
110546940  Ccnd1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
110558913  Kras; GTPase KRas isoform X1 [KO:K07827]
110565112  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110556252  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110548394  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110553683  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110549145  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110563512  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110551603  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110545060  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
110541705  Araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
110545779  Braf; serine/threonine-protein kinase B-raf isoform X8 [KO:K04365] [EC:2.7.11.1]
110550814  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
110559000  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110555605  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110559727  Jun; transcription factor Jun [KO:K04448]
110546962  Fos; protein c-Fos [KO:K04379]
110549995  Ralgds; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
110545330  Rala; ras-related protein Ral-A [KO:K07834]
110546412  Ralb; ras-related protein Ral-B [KO:K07835]
110557417  Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
110548466  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
110548820  Rac3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
110540728  transforming protein RhoA-like isoform X1 [KO:K04513]
110565123  Rhoa; transforming protein RhoA isoform X2 [KO:K04513]
110552285  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110557386  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110562875  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110562838  Dcc; netrin receptor DCC isoform X1 [KO:K06765]
132653623  Casp3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
110566349  Appl1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
110561197  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
110549244  Tgfb2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
110558214  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
110551136  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
110547249  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
110550301  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
110557887  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
110550715  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
110559312  Mlh1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
110552895  Msh2; DNA mismatch repair protein Msh2 [KO:K08735]
110546895  Msh3; DNA mismatch repair protein Msh3 isoform X1 [KO:K08736]
110561037  Msh6; DNA mismatch repair protein Msh6 isoform X1 [KO:K08737]
110560658  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
110555473  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 isoform X1 [KO:K10131]
110559284  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
110561311  Bbc3; bcl-2-binding component 3 isoform X2 [KO:K10132]
110557800  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110545164  cytochrome c, somatic [KO:K08738]
110555979  cytochrome c, testis-specific [KO:K08738]
110563439  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
110559601  cytochrome c, somatic-like [KO:K08738]
110549868  LOW QUALITY PROTEIN: cytochrome c, somatic-like [KO:K08738]
110552819  cytochrome c, somatic-like [KO:K08738]
110555127  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110546586  Cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
110555604  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110558423  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X2 [KO:K04402]
110559073  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110543676  Bak1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
110550733  Ddb2; DNA damage-binding protein 2 [KO:K10140]
110563772  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
110553196  Egf; pro-epidermal growth factor [KO:K04357]
110547163  Tgfa; protransforming growth factor alpha [KO:K08774]
110565263  Ereg; proepiregulin [KO:K09784]
110560146  Areg; amphiregulin [KO:K09782]
110539539  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
110547825  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
110547073  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
110556913  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110553931  Hras; GTPase HRas isoform X1 [KO:K02833]
110544642  GTPase NRas [KO:K07828]
110544765  Nras; GTPase NRas [KO:K07828]
110548161  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110553742  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
110560360  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
mun04010  MAPK signaling pathway
mun04012  ErbB signaling pathway
mun04110  Cell cycle
mun04115  p53 signaling pathway
mun04150  mTOR signaling pathway
mun04151  PI3K-Akt signaling pathway
mun04210  Apoptosis
mun04310  Wnt signaling pathway
mun04350  TGF-beta signaling pathway
KO pathway
ko05210   
LinkDB

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