KEGG   PATHWAY: vlg05217
Entry
vlg05217                    Pathway                                
Name
Basal cell carcinoma - Vulpes lagopus (Arctic fox)
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
vlg05217  Basal cell carcinoma
vlg05217

Organism
Vulpes lagopus (Arctic fox) [GN:vlg]
Gene
121499929  TP53; cellular tumor antigen p53 [KO:K04451]
121473591  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
121486283  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
121479706  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
121495322  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
121484229  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
121497413  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
121472218  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
121489193  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
121488899  SHH; sonic hedgehog protein isoform X1 [KO:K11988]
121484106  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
121474672  SMO; smoothened homolog isoform X1 [KO:K06226]
121488658  KIF7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
121484547  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
121491172  GLI1; zinc finger protein GLI1 isoform X1 [KO:K16797]
121482121  GLI2; zinc finger protein GLI2 [KO:K16798]
121471819  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
121478407  BMP2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
121493806  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
121480912  hedgehog-interacting protein isoform X1 [KO:K06231]
121481639  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
121480178  WNT1; proto-oncogene Wnt-1 isoform X1 [KO:K03209]
121474438  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
121490731  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
121474007  WNT3; proto-oncogene Wnt-3 [KO:K00312]
121474467  WNT3A; protein Wnt-3a [KO:K00312]
121498205  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
121479913  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
121495641  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
121480717  WNT6; protein Wnt-6 [KO:K00445]
121490476  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
121495152  WNT7A; protein Wnt-7a [KO:K00572]
121476849  WNT8B; protein Wnt-8b [KO:K00714]
121495235  WNT8A; protein Wnt-8a [KO:K00714]
121474006  WNT9B; protein Wnt-9b [KO:K01064]
121475053  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
121480841  WNT10A; protein Wnt-10a [KO:K01357]
121480042  WNT10B; protein Wnt-10b [KO:K01357]
121475935  WNT11; protein Wnt-11 [KO:K01384]
121474824  WNT16; protein Wnt-16 [KO:K01558]
121480659  FZD7; frizzled-7 isoform X1 [KO:K02432]
121474752  FZD1; frizzled-1 [KO:K02432]
121472594  FZD2; frizzled-2 [KO:K02235]
121498183  FZD3; frizzled-3 isoform X1 [KO:K02329]
121476036  FZD4; frizzled-4 isoform X1 [KO:K02354]
121480532  FZD5; frizzled-5 [KO:K02375]
121498057  FZD8; frizzled-8 [KO:K02375]
121498902  FZD6; frizzled-6 isoform X1 [KO:K02376]
121475662  FZD10; frizzled-10 [KO:K02842]
121486703  FZD9; frizzled-9 [KO:K02842]
121477470  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
121499761  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
121499953  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
121489623  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
121486746  AXIN1; axin-1 isoform X1 [KO:K02157]
121473774  AXIN2; axin-2 isoform X1 [KO:K04385]
121489860  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
121495587  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
121478755  CTNNB1; catenin beta-1 [KO:K02105]
121495797  TCF7; transcription factor 7 isoform X1 [KO:K02620]
121490511  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
121485032  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
121493895  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [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
vlg04110  Cell cycle
vlg04115  p53 signaling pathway
vlg04310  Wnt signaling pathway
vlg04340  Hedgehog signaling pathway
vlg04350  TGF-beta signaling pathway
KO pathway
ko05217   
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