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KEGG   PATHWAY: hsa05217
hsa05217                    Pathway                                
Basal cell carcinoma - Homo sapiens (human)
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.
Human Diseases; Cancer: specific types
Pathway map
hsa05217  Basal cell carcinoma

nt06217  HH signaling
nt06240  Transcription
nt06260  Colorectal cancer
nt06261  Gastric cancer
nt06262  Pancreatic cancer
nt06263  Hepatocellular carcinoma
nt06265  Bladder cancer
nt06266  Non-small cell lung cancer
nt06267  Small cell lung cancer
nt06268  Melanoma
nt06269  Basal cell carcinoma
nt06270  Breast cancer
nt06271  Endometrial cancer
nt06273  Glioma
nt06274  Thyroid cancer
nt06276  Chronic myeloid leukemia
N00010  Mutation-inactivated PTCH1 to Hedgehog signaling pathway
N00017  Mutation-activated SMO to Hedgehog signaling pathway
N00115  Mutation-inactivated TP53 to transcription
H00039  Basal cell carcinoma
D09992  Vismodegib (USAN/INN)
D10119  Sonidegib (USAN/INN)
D10729  Sonidegib phosphate (USAN)
Homo sapiens (human) [GN:hsa]
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:]
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:]
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]
C00187  Cholesterol
Tilli CM, Van Steensel MA, Krekels GA, Neumann HA, Ramaekers FC.
Molecular aetiology and pathogenesis of basal cell carcinoma.
Br J Dermatol 152:1108-24 (2005)
Saldanha G, Fletcher A, Slater DN.
Basal cell carcinoma: a dermatopathological and molecular biological update.
Br J Dermatol 148:195-202 (2003)
Daya-Grosjean L, Couve-Privat S.
Sonic hedgehog signaling in basal cell carcinomas.
Cancer Lett 225:181-92 (2005)
Tsai KY, Tsao H.
The genetics of skin cancer.
Am J Med Genet C Semin Med Genet 131C:82-92 (2004)
Athar M, Tang X, Lee JL, Kopelovich L, Kim AL.
Hedgehog signalling in skin development and cancer.
Exp Dermatol 15:667-77 (2006)
Rubin AI, Chen EH, Ratner D.
Basal-cell carcinoma.
N Engl J Med 353:2262-9 (2005)
Saldanha G.
The Hedgehog signalling pathway and cancer.
Saldanha G, Ghura V, Potter L, Fletcher A.
Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation.
Br J Dermatol 151:157-64 (2004)
Pasca di Magliano M, Hebrok M.
Hedgehog signalling in cancer formation and maintenance.
Nat Rev Cancer 3:903-11 (2003)
Reifenberger J, Wolter M, Knobbe CB, Kohler B, Schonicke A, Scharwachter C, Kumar K, Blaschke B, Ruzicka T, Reifenberger G.
Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas.
Br J Dermatol 152:43-51 (2005)
Cohen MM Jr.
The hedgehog signaling network.
Am J Med Genet A 123:5-28 (2003)
Yamazaki F, Aragane Y, Kawada A, Tezuka T.
Immunohistochemical detection for nuclear beta-catenin in sporadic basal cell carcinoma.
Br J Dermatol 145:771-7 (2001)
Erb P, Ji J, Wernli M, Kump E, Glaser A, Buchner SA.
Role of apoptosis in basal cell and squamous cell carcinoma formation.
Immunol Lett 100:68-72 (2005)
Toftgard R.
Hedgehog signalling in cancer.
Cell Mol Life Sci 57:1720-31 (2000)
Wu F, Zhang Y, Sun B, McMahon AP, Wang Y
Hedgehog Signaling: From Basic Biology to Cancer Therapy.
Cell Chem Biol 24:252-280 (2017)
Otsuka A, Levesque MP, Dummer R, Kabashima K
Hedgehog signaling in basal cell carcinoma.
J Dermatol Sci 78:95-100 (2015)
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04310  Wnt signaling pathway
hsa04340  Hedgehog signaling pathway
hsa04350  TGF-beta signaling pathway
KO pathway

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