KEGG   PATHWAY: hsa05217
Entry
hsa05217                    Pathway                                
Name
Basal cell carcinoma - Homo sapiens (human)
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
hsa05217  Basal cell carcinoma
hsa05217

Network
  Element
N00010  Mutation-inactivated PTCH1 to Hedgehog signaling pathway
N00017  Mutation-activated SMO to Hedgehog signaling pathway
N00115  Mutation-inactivated TP53 to transcription
Disease
H00039  Basal cell carcinoma
Drug
D09992  Vismodegib (USAN/INN)
D10119  Sonidegib (USAN/INN)
D10729  Sonidegib phosphate (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
7157  TP53; tumor protein p53 [KO:K04451]
1026  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
1647  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
4616  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
10912  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
578  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
1643  DDB2; damage specific DNA binding protein 2 [KO:K10140]
51426  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
6469  SHH; sonic hedgehog signaling molecule [KO:K11988]
5727  PTCH1; patched 1 [KO:K06225]
6608  SMO; smoothened, frizzled class receptor [KO:K06226]
374654  KIF7; kinesin family member 7 [KO:K18806]
51684  SUFU; SUFU negative regulator of hedgehog signaling [KO:K06229]
2735  GLI1; GLI family zinc finger 1 [KO:K16797]
2736  GLI2; GLI family zinc finger 2 [KO:K16798]
2737  GLI3; GLI family zinc finger 3 [KO:K06230]
650  BMP2; bone morphogenetic protein 2 [KO:K21283]
652  BMP4; bone morphogenetic protein 4 [KO:K04662]
64399  HHIP; hedgehog interacting protein [KO:K06231]
8643  PTCH2; patched 2 [KO:K11101]
7471  WNT1; Wnt family member 1 [KO:K03209]
7472  WNT2; Wnt family member 2 [KO:K00182]
7482  WNT2B; Wnt family member 2B [KO:K00182]
7473  WNT3; Wnt family member 3 [KO:K00312]
89780  WNT3A; Wnt family member 3A [KO:K00312]
54361  WNT4; Wnt family member 4 [KO:K00408]
7474  WNT5A; Wnt family member 5A [KO:K00444]
81029  WNT5B; Wnt family member 5B [KO:K00444]
7475  WNT6; Wnt family member 6 [KO:K00445]
7476  WNT7A; Wnt family member 7A [KO:K00572]
7477  WNT7B; Wnt family member 7B [KO:K00572]
7478  WNT8A; Wnt family member 8A [KO:K00714]
7479  WNT8B; Wnt family member 8B [KO:K00714]
7483  WNT9A; Wnt family member 9A [KO:K01064]
7484  WNT9B; Wnt family member 9B [KO:K01064]
7480  WNT10B; Wnt family member 10B [KO:K01357]
80326  WNT10A; Wnt family member 10A [KO:K01357]
7481  WNT11; Wnt family member 11 [KO:K01384]
51384  WNT16; Wnt family member 16 [KO:K01558]
8321  FZD1; frizzled class receptor 1 [KO:K02432]
8324  FZD7; frizzled class receptor 7 [KO:K02432]
2535  FZD2; frizzled class receptor 2 [KO:K02235]
7976  FZD3; frizzled class receptor 3 [KO:K02329]
8322  FZD4; frizzled class receptor 4 [KO:K02354]
7855  FZD5; frizzled class receptor 5 [KO:K02375]
8325  FZD8; frizzled class receptor 8 [KO:K02375]
8323  FZD6; frizzled class receptor 6 [KO:K02376]
11211  FZD10; frizzled class receptor 10 [KO:K02842]
8326  FZD9; frizzled class receptor 9 [KO:K02842]
1857  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
1856  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
1855  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
8312  AXIN1; axin 1 [KO:K02157]
8313  AXIN2; axin 2 [KO:K04385]
324  APC; APC regulator of WNT signaling pathway [KO:K02085]
10297  APC2; APC regulator of WNT signaling pathway 2 [KO:K02085]
1499  CTNNB1; catenin beta 1 [KO:K02105]
6932  TCF7; transcription factor 7 [KO:K02620]
83439  TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
Compound
C00187  Cholesterol
Reference
PMID:15948971
  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
PMID:12588368
  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
PMID:15978322
  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
PMID:15468170
  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
PMID:16881963
  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
PMID:16306523
  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
PMID:11276000
  Authors
Saldanha G.
  Title
The Hedgehog signalling pathway and cancer.
  Journal
J Pathol 193:427-32 (2001)
DOI:10.1002/1096-9896(2000)9999:9999<::AID-PATH815>3.0.CO;2-N
Reference
PMID:15270885
  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
PMID:14737121
  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
PMID:15656799
  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
PMID:14556242
  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
PMID:11736900
  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
PMID:16054233
  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
PMID:11130178
  Authors
Toftgard R.
  Title
Hedgehog signalling in cancer.
  Journal
Cell Mol Life Sci 57:1720-31 (2000)
DOI:10.1007/PL00000654
Reference
PMID:28286127
  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
PMID:25766766
  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
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04310  Wnt signaling pathway
hsa04340  Hedgehog signaling pathway
hsa04350  TGF-beta signaling pathway
KO pathway
ko05217   
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