KEGG PATHWAY: hsa05217

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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

Network

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

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

All links

Network (3)   
   KEGG NETWORK (3)   
Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (63)   
   KEGG GENES (63)   
All databases (68)   

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