KEGG   PATHWAY: mjv05210
Entry
mjv05210                    Pathway                                
Name
Colorectal cancer - Manis javanica (Malayan pangolin)
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
mjv05210  Colorectal cancer
mjv05210

Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108389003  GSK3B; glycogen synthase kinase-3 beta isoform X5 [KO:K03083] [EC:2.7.11.26]
108408106  AXIN1; axin-1 isoform X1 [KO:K02157]
108392410  AXIN2; axin-2 isoform X1 [KO:K04385]
108387548  CTNNB1; catenin beta-1 [KO:K02105]
108408639  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
108404758  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
108406081  TCF7; transcription factor 7 isoform X1 [KO:K02620]
108405898  TCF7L1; transcription factor 7-like 1 [KO:K04490]
108408173  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
108405595  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
108407801  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
108399996  MYC; myc proto-oncogene protein [KO:K04377]
108388480  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
108395842  KRAS; GTPase KRas isoform X1 [KO:K07827]
108406544  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108390365  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108400388  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108383561  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108390475  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
108395975  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
108397433  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108390484  AKT2; RAC-beta serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
108393746  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108407571  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
108398550  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
108387830  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
108394305  LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf-like [KO:K04365] [EC:2.7.11.1]
108394341  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
108392139  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108385046  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
108398454  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108400663  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108386817  JUN; transcription factor AP-1 [KO:K04448]
108402534  FOS; proto-oncogene c-Fos [KO:K04379]
108388220  RALGDS; ral guanine nucleotide dissociation stimulator isoform X2 [KO:K08732]
108393225  RALA; ras-related protein Ral-A [KO:K07834]
108400050  RALB; ras-related protein Ral-B [KO:K07835]
108407595  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
108392664  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
108383250  transforming protein RhoA [KO:K04513]
108396943  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
108384893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108385635  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108383934  DCC; netrin receptor DCC [KO:K06765]
108389793  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
108397387  APPL1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
108383720  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
108403151  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
108404608  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
108394148  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
108391859  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
108400736  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
108404778  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
108394195  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
108405876  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
108391861  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
108387749  MSH3; DNA mismatch repair protein Msh3 [KO:K08736]
108394002  MSH6; DNA mismatch repair protein Msh6 [KO:K08737]
108400315  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
118969429  apoptosis regulator BAX [KO:K02159]
108390232  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
108394828  BCL2L11; bcl-2-like protein 11 isoform X5 [KO:K16341]
108398862  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
108385222  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
108393483  cytochrome c-like [KO:K08738]
108396077  cytochrome c [KO:K08738]
108404266  TP53; cellular tumor antigen p53 [KO:K04451]
118974052  cellular tumor antigen p53 [KO:K04451]
108385913  cyclin-dependent kinase inhibitor 1 [KO:K06625]
118970122  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
108393260  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
108404892  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
108393837  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
108402940  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
108388647  DDB2; LOW QUALITY PROTEIN: DNA damage-binding protein 2 [KO:K10140]
108408163  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
108408073  EGF; pro-epidermal growth factor [KO:K04357]
108388206  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
108409106  AREG; amphiregulin [KO:K09782]
108397962  EGFR; epidermal growth factor receptor isoform X5 [KO:K04361] [EC:2.7.10.1]
108400653  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
108391894  SOS2; son of sevenless homolog 2 [KO:K03099]
108385648  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
108408627  HRAS; GTPase HRas isoform X1 [KO:K02833]
118967667  GTPase HRas-like isoform X1 [KO:K02833]
108398047  NRAS; GTPase NRas [KO:K07828]
108390746  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
108393161  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
108401175  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
mjv04010  MAPK signaling pathway
mjv04012  ErbB signaling pathway
mjv04110  Cell cycle
mjv04115  p53 signaling pathway
mjv04150  mTOR signaling pathway
mjv04151  PI3K-Akt signaling pathway
mjv04210  Apoptosis
mjv04310  Wnt signaling pathway
mjv04350  TGF-beta signaling pathway
KO pathway
ko05210   
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