KEGG   PATHWAY: ngi05210
Entry
ngi05210                    Pathway                                
Name
Colorectal cancer - Nannospalax galili (Upper Galilee mountains blind mole rat)
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
ngi05210  Colorectal cancer
ngi05210

Organism
Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
Gene
103741948  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103748223  Axin1; axin 1 [KO:K02157]
103742203  Axin2; axin 2 [KO:K04385]
103747127  Ctnnb1; catenin beta 1 [KO:K02105]
103737324  Apc2; APC2, WNT signaling pathway regulator [KO:K02085]
103735168  Apc; APC, WNT signaling pathway regulator [KO:K02085]
103729786  Tcf7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
103739783  Tcf7l1; transcription factor 7 like 1 [KO:K04490]
103731749  Tcf7l2; transcription factor 7 like 2 [KO:K04491]
103742515  Lef1; lymphoid enhancer binding factor 1 [KO:K04492]
103747285  Birc5; baculoviral IAP repeat containing 5 [KO:K08731]
103743920  Myc; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
103751498  Ccnd1; cyclin D1 [KO:K04503]
103736717  Kras; KRAS proto-oncogene, GTPase [KO:K07827]
103738596  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103733121  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103742946  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103738715  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103726879  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103730305  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103746884  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103750757  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103752536  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103738795  Bad; BCL2 associated agonist of cell death [KO:K02158]
103725336  Casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]
103741627  Araf; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
103726107  Braf; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103751450  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103736801  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103737276  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103741442  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103726390  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103737138  Jun; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
103747342  Fos; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
103742830  Ralgds; ral guanine nucleotide dissociation stimulator [KO:K08732]
103736746  Rala; RAS like proto-oncogene A [KO:K07834]
103732313  Ralb; RAS like proto-oncogene B [KO:K07835]
103726484  Rac1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
103748617  Rac2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
103743359  transforming protein RhoA-like [KO:K04513]
103750189  Rhoa; ras homolog family member A [KO:K04513]
103735023  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103748972  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103749366  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103725530  Dcc; DCC netrin 1 receptor [KO:K06765]
103744668  caspase-3-like [KO:K02187] [EC:3.4.22.56]
103750475  Casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
103747007  Appl1; adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 [KO:K08733]
103751514  Tgfb1; transforming growth factor beta 1 [KO:K13375]
103728817  Tgfb2; transforming growth factor beta 2 [KO:K13376]
103739777  Tgfb3; transforming growth factor beta 3 [KO:K13377]
103744902  Tgfbr1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
103744639  Tgfbr2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
103727836  Smad2; SMAD family member 2 [KO:K04500]
103736807  Smad3; SMAD family member 3 [KO:K23605]
103726635  Smad4; SMAD family member 4 [KO:K04501]
103731918  Mlh1; mutL homolog 1 [KO:K08734]
103725741  Msh2; mutS homolog 2 [KO:K08735]
103750270  Msh3; mutS homolog 3 [KO:K08736]
103725738  Msh6; mutS homolog 6 [KO:K08737]
103743639  Bax; BCL2 associated X, apoptosis regulator [KO:K02159]
103739615  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
103750963  Bcl2l11; BCL2 like 11 [KO:K16341]
103724866  Bbc3; BCL2 binding component 3 [KO:K10132]
103740099  Bcl2; BCL2, apoptosis regulator [KO:K02161]
103740800  cytochrome c, somatic [KO:K08738]
103751785  cytochrome c, testis-specific [KO:K08738]
103752115  Tp53; tumor protein p53 [KO:K04451]
103739652  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
103737285  Gadd45b; growth arrest and DNA damage inducible beta [KO:K04402]
103743354  Gadd45a; growth arrest and DNA damage inducible alpha [KO:K04402]
103751225  Gadd45g; growth arrest and DNA damage inducible gamma [KO:K04402]
103739733  Bak1; BCL2 antagonist/killer 1 [KO:K14021]
103742505  Ddb2; damage specific DNA binding protein 2 [KO:K10140]
103736569  Polk; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
103742642  Egf; epidermal growth factor [KO:K04357]
103725901  Tgfa; transforming growth factor alpha [KO:K08774]
103742473  Ereg; epiregulin [KO:K09784]
103742434  Areg; amphiregulin [KO:K09782]
103748852  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103732729  Grb2; growth factor receptor bound protein 2 [KO:K04364]
103743944  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103731514  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103751075  Hras; HRas proto-oncogene, GTPase [KO:K02833]
103734938  Nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103732897  Mtor; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103741760  Rps6kb1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
103725586  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
ngi04010  MAPK signaling pathway
ngi04012  ErbB signaling pathway
ngi04110  Cell cycle
ngi04115  p53 signaling pathway
ngi04150  mTOR signaling pathway
ngi04151  PI3K-Akt signaling pathway
ngi04210  Apoptosis
ngi04310  Wnt signaling pathway
ngi04350  TGF-beta signaling pathway
KO pathway
ko05210   
LinkDB

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