KEGG   PATHWAY: nle05217
Entry
nle05217                    Pathway                                

Name
Basal cell carcinoma - Nomascus leucogenys (northern white-cheeked gibbon)
Description
Cancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare familial syndrome basal cell nevus syndrome (BCNS, or Gorlin syndrome) that predisposes to development of BCC. In addition, there is strong epidemiological and genetic evidence that demonstrates UV exposure as a risk factor of prime importance. The development of basal cell carcinoma is associated with constitutive activation of sonic hedgehog signaling. The mutations in SMOH, PTCH1, and SHH in BCCs result in continuous activation of target genes. At a cellular level, sonic hedgehog signaling promotes cell proliferation. Mutations in TP53 are also found with high frequency (>50%) in sporadic BCC.
Class
Human Diseases; Cancer: specific types
Pathway map
nle05217  Basal cell carcinoma
nle05217

Organism
Nomascus leucogenys (northern white-cheeked gibbon) [GN:nle]
Gene
100583326  TP53; cellular tumor antigen p53 [KO:K04451]
100599083  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100593432  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100583800  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
115830865  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100593013  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100588483  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100605065  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100598341  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
100582247  SHH; sonic hedgehog protein isoform X1 [KO:K11988]
100581789  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
100585701  SMO; smoothened homolog isoform X1 [KO:K06226]
100587965  KIF7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
100593147  SUFU; suppressor of fused homolog isoform X2 [KO:K06229]
100599158  GLI1; zinc finger protein GLI1 [KO:K16797]
100593982  GLI2; zinc finger protein GLI2 [KO:K16798]
100589630  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
100586297  BMP2; bone morphogenetic protein 2 [KO:K21283]
100586277  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
100602907  HHIP; hedgehog-interacting protein [KO:K06231]
100591053  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
100587307  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100607954  WNT2B; protein Wnt-2b isoform X2 [KO:K00182]
100600353  WNT2; protein Wnt-2 [KO:K00182]
100606846  WNT3A; protein Wnt-3a isoform X2 [KO:K00312]
100599381  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100604353  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
100602014  WNT5A; protein Wnt-5a [KO:K00444]
100596686  WNT5B; protein Wnt-5b [KO:K00444]
100606818  WNT6; protein Wnt-6 [KO:K00445]
100579580  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
100593900  WNT7A; protein Wnt-7a [KO:K00572]
100586052  WNT8A; protein Wnt-8a isoform X2 [KO:K00714]
100603238  WNT8B; protein Wnt-8b [KO:K00714]
100606502  WNT9A; protein Wnt-9a [KO:K01064]
100602760  WNT9B; protein Wnt-9b isoform X1 [KO:K01064]
100607164  WNT10A; protein Wnt-10a [KO:K01357]
100587640  WNT10B; protein Wnt-10b [KO:K01357]
100594864  WNT11; protein Wnt-11 [KO:K01384]
100605294  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
100597685  FZD7; frizzled-7 [KO:K02432]
100605346  FZD1; frizzled-1 [KO:K02432]
100580071  FZD2; frizzled-2 [KO:K02235]
100589994  FZD3; frizzled-3 [KO:K02329]
100588311  FZD4; frizzled-4 [KO:K02354]
100589091  FZD5; frizzled-5 [KO:K02375]
100593717  FZD8; frizzled-8 [KO:K02375]
100603705  FZD6; frizzled-6 [KO:K02376]
100607762  FZD10; frizzled-10 [KO:K02842]
100592375  FZD9; frizzled-9 [KO:K02842]
100585595  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
100583216  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
100593186  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
100606885  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101179424  AXIN1; axin-1 isoform X1 [KO:K02157]
100589482  AXIN2; axin-2 isoform X1 [KO:K04385]
100602025  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
100585467  APC; adenomatous polyposis coli protein isoform X3 [KO:K02085]
100583002  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
100595737  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
100601518  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100605701  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
100593051  LEF1; lymphoid enhancer-binding factor 1 isoform X3 [KO:K04492]
Compound
C00187  Cholesterol
Reference
  Authors
Tilli CM, Van Steensel MA, Krekels GA, Neumann HA, Ramaekers FC.
  Title
Molecular aetiology and pathogenesis of basal cell carcinoma.
  Journal
Br J Dermatol 152:1108-24 (2005)
DOI:10.1111/j.1365-2133.2005.06587.x
Reference
  Authors
Saldanha G, Fletcher A, Slater DN.
  Title
Basal cell carcinoma: a dermatopathological and molecular biological update.
  Journal
Br J Dermatol 148:195-202 (2003)
DOI:10.1046/j.1365-2133.2003.05151.x
Reference
  Authors
Daya-Grosjean L, Couve-Privat S.
  Title
Sonic hedgehog signaling in basal cell carcinomas.
  Journal
Cancer Lett 225:181-92 (2005)
DOI:10.1016/j.canlet.2004.10.003
Reference
  Authors
Tsai KY, Tsao H.
  Title
The genetics of skin cancer.
  Journal
Am J Med Genet C Semin Med Genet 131C:82-92 (2004)
DOI:10.1002/ajmg.c.30037
Reference
  Authors
Athar M, Tang X, Lee JL, Kopelovich L, Kim AL.
  Title
Hedgehog signalling in skin development and cancer.
  Journal
Exp Dermatol 15:667-77 (2006)
DOI:10.1111/j.1600-0625.2006.00473.x
Reference
  Authors
Rubin AI, Chen EH, Ratner D.
  Title
Basal-cell carcinoma.
  Journal
N Engl J Med 353:2262-9 (2005)
DOI:10.1056/NEJMra044151
Reference
  Authors
Saldanha G.
  Title
The Hedgehog signalling pathway and cancer.
  Journal
Reference
  Authors
Saldanha G, Ghura V, Potter L, Fletcher A.
  Title
Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation.
  Journal
Br J Dermatol 151:157-64 (2004)
DOI:10.1111/j.1365-2133.2004.06048.x
Reference
  Authors
Pasca di Magliano M, Hebrok M.
  Title
Hedgehog signalling in cancer formation and maintenance.
  Journal
Nat Rev Cancer 3:903-11 (2003)
DOI:10.1038/nrc1229
Reference
  Authors
Reifenberger J, Wolter M, Knobbe CB, Kohler B, Schonicke A, Scharwachter C, Kumar K, Blaschke B, Ruzicka T, Reifenberger G.
  Title
Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas.
  Journal
Br J Dermatol 152:43-51 (2005)
DOI:10.1111/j.1365-2133.2005.06353.x
Reference
  Authors
Cohen MM Jr.
  Title
The hedgehog signaling network.
  Journal
Am J Med Genet A 123:5-28 (2003)
DOI:10.1002/ajmg.a.20495
Reference
  Authors
Yamazaki F, Aragane Y, Kawada A, Tezuka T.
  Title
Immunohistochemical detection for nuclear beta-catenin in sporadic basal cell carcinoma.
  Journal
Br J Dermatol 145:771-7 (2001)
DOI:10.1046/j.1365-2133.2001.04468.x
Reference
  Authors
Erb P, Ji J, Wernli M, Kump E, Glaser A, Buchner SA.
  Title
Role of apoptosis in basal cell and squamous cell carcinoma formation.
  Journal
Immunol Lett 100:68-72 (2005)
DOI:10.1016/j.imlet.2005.06.008
Reference
  Authors
Toftgard R.
  Title
Hedgehog signalling in cancer.
  Journal
Cell Mol Life Sci 57:1720-31 (2000)
DOI:10.1007/PL00000654
Reference
  Authors
Wu F, Zhang Y, Sun B, McMahon AP, Wang Y
  Title
Hedgehog Signaling: From Basic Biology to Cancer Therapy.
  Journal
Cell Chem Biol 24:252-280 (2017)
DOI:10.1016/j.chembiol.2017.02.010
Reference
  Authors
Otsuka A, Levesque MP, Dummer R, Kabashima K
  Title
Hedgehog signaling in basal cell carcinoma.
  Journal
J Dermatol Sci 78:95-100 (2015)
DOI:10.1016/j.jdermsci.2015.02.007
Related
pathway
nle04110  Cell cycle
nle04115  p53 signaling pathway
nle04310  Wnt signaling pathway
nle04340  Hedgehog signaling pathway
nle04350  TGF-beta signaling pathway
KO pathway
ko05217   
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