KEGG   PATHWAY: ppam05210
Entry
ppam05210                   Pathway                                
Name
Colorectal cancer - Pteronotus mesoamericanus (Parnell's mustached 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
ppam05210  Colorectal cancer
ppam05210

Disease
H00020  Colorectal cancer
Organism
Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]
Gene
129062822  [KO:K08738]
129062984  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
129063346  RALA; ras-related protein Ral-A [KO:K07834]
129063946  NRAS; GTPase NRas [KO:K07828]
129064134  [KO:K03099]
129064154  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
129064157  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129064891  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
129065007  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
129065223  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
129065589  MSH6; DNA mismatch repair protein Msh6 isoform X1 [KO:K08737]
129065621  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
129065729  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
129065732  FOS; protein c-Fos [KO:K04379]
129066034  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
129066231  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129066685  TCF7; transcription factor 7 isoform X1 [KO:K02620]
129066993  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
129067419  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
129068140  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
129068523  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
129068535  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
129068612  BAD; bcl2-associated agonist of cell death [KO:K02158]
129068919  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
129069407  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129069640  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129069687  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
129069921  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
129070231  AXIN2; axin-2 isoform X1 [KO:K04385]
129070771  JUN; transcription factor Jun [KO:K04448]
129071250  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
129071563  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
129071736  RALB; ras-related protein Ral-B isoform X1 [KO:K07835]
129072137  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
129072290  TP53; cellular tumor antigen p53 [KO:K04451]
129072973  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
129073033  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129073113  HRAS; GTPase HRas isoform X1 [KO:K02833]
129073949  TCF7L1; transcription factor 7-like 1 [KO:K04490]
129074464  [KO:K04513]
129074590  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129074622  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
129074652  MSH3; DNA mismatch repair protein Msh3 [KO:K08736]
129074969  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129075586  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
129075656  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
129075675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129076577  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129076641  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129076675  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
129077183  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
129078069  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129078155  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129078413  [KO:K04392]
129078704  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
129078725  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
129078727  DCC; netrin receptor DCC [KO:K06765]
129078764  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129078902  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 isoform X1 [KO:K10131]
129079186  RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
129079398  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
129081112  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
129081256  AXIN1; axin-1 isoform X1 [KO:K02157]
129081363  TGFA; protransforming growth factor alpha [KO:K08774]
129081434  DDB2; DNA damage-binding protein 2 [KO:K10140]
129081677  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
129082218  [KO:K08738]
129082291  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
129082775  BBC3; bcl-2-binding component 3 [KO:K10132]
129082924  BAX; apoptosis regulator BAX [KO:K02159]
129083450  [KO:K08738]
129083908  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
129084081  MYC; myc proto-oncogene protein [KO:K04377]
129084433  [KO:K08738]
129084969  KRAS; GTPase KRas isoform X1 [KO:K07827]
129085245  AREG; amphiregulin [KO:K09782]
129085287  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
129085299  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
129085376  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
129085967  [KO:K04513]
129086248  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129086565  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
129086587  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
129086649  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
129087491  EREG; proepiregulin [KO:K09784]
129087688  RHOA; transforming protein RhoA [KO:K04513]
129087856  MLH1; DNA mismatch repair protein Mlh1 [KO:K08734]
129088092  APPL1; DCC-interacting protein 13-alpha isoform X1 [KO:K08733]
129088202  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
129088214  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
129088291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129088423  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [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
ppam04010  MAPK signaling pathway
ppam04012  ErbB signaling pathway
ppam04110  Cell cycle
ppam04115  p53 signaling pathway
ppam04150  mTOR signaling pathway
ppam04151  PI3K-Akt signaling pathway
ppam04210  Apoptosis
ppam04310  Wnt signaling pathway
ppam04350  TGF-beta signaling pathway
KO pathway
ko05210   

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