Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMG07H5)

• DOT Name: Protein patched homolog 1 (PTCH1)
• Synonyms: PTC; PTC1
• Gene Name: PTCH1
• Related Disease:
  Basal cell neoplasm
  Basal cell nevus syndrome
  Hereditary hemochromatosis
  Holoprosencephaly 7
  Rhabdomyosarcoma
  Advanced cancer
  Anterior segment dysgenesis 7
  Anxiety
  Basal cell carcinoma
  Brachydactyly
  Brain neoplasm
  Breast carcinoma
  Epithelial ovarian cancer
  Gastrointestinal stromal tumour
  HIV infectious disease
  Isolated cleft palate
  Oculodentodigital dysplasia
  Ovarian cancer
  Pancreatic tumour
  Primitive neuroectodermal tumor
  Retinopathy
  Squamous cell carcinoma
  Subarachnoid hemorrhage
  Wilms tumor
  Asthma
  Brain cancer
  Isolated cleft lip
  Isolated congenital microcephaly
  Megalencephaly
  Melanocytic nevus
  Hereditary neoplastic syndrome
  Carcinoma
  Holoprosencephaly
  Rieger anomaly
• UniProt ID: PTC1_HUMAN
• PDB ID: 6DMB; 6DMO; 6DMY; 6E1H; 6N7G; 6N7H; 6N7K; 6OEU; 6OEV; 6RMG; 6RTW; 6RTX; 6RTY; 6RVC; 6RVD
• Pfam ID: PF02460
• Sequence:
  MASAGNAAEPQDRGGGGSGCIGAPGRPAGGGRRRRTGGLRRAAAPDRDYLHRPSYCDAAF
  ALEQISKGKATGRKAPLWLRAKFQRLLFKLGCYIQKNCGKFLVVGLLIFGAFAVGLKAAN
  LETNVEELWVEVGGRVSRELNYTRQKIGEEAMFNPQLMIQTPKEEGANVLTTEALLQHLD
  SALQASRVHVYMYNRQWKLEHLCYKSGELITETGYMDQIIEYLYPCLIITPLDCFWEGAK
  LQSGTAYLLGKPPLRWTNFDPLEFLEELKKINYQVDSWEEMLNKAEVGHGYMDRPCLNPA
  DPDCPATAPNKNSTKPLDMALVLNGGCHGLSRKYMHWQEELIVGGTVKNSTGKLVSAHAL
  QTMFQLMTPKQMYEHFKGYEYVSHINWNEDKAAAILEAWQRTYVEVVHQSVAQNSTQKVL
  SFTTTTLDDILKSFSDVSVIRVASGYLLMLAYACLTMLRWDCSKSQGAVGLAGVLLVALS
  VAAGLGLCSLIGISFNAATTQVLPFLALGVGVDDVFLLAHAFSETGQNKRIPFEDRTGEC
  LKRTGASVALTSISNVTAFFMAALIPIPALRAFSLQAAVVVVFNFAMVLLIFPAILSMDL
  YRREDRRLDIFCCFTSPCVSRVIQVEPQAYTDTHDNTRYSPPPPYSSHSFAHETQITMQS
  TVQLRTEYDPHTHVYYTTAEPRSEISVQPVTVTQDTLSCQSPESTSSTRDLLSQFSDSSL
  HCLEPPCTKWTLSSFAEKHYAPFLLKPKAKVVVIFLFLGLLGVSLYGTTRVRDGLDLTDI
  VPRETREYDFIAAQFKYFSFYNMYIVTQKADYPNIQHLLYDLHRSFSNVKYVMLEENKQL
  PKMWLHYFRDWLQGLQDAFDSDWETGKIMPNNYKNGSDDGVLAYKLLVQTGSRDKPIDIS
  QLTKQRLVDADGIINPSAFYIYLTAWVSNDPVAYAASQANIRPHRPEWVHDKADYMPETR
  LRIPAAEPIEYAQFPFYLNGLRDTSDFVEAIEKVRTICSNYTSLGLSSYPNGYPFLFWEQ
  YIGLRHWLLLFISVVLACTFLVCAVFLLNPWTAGIIVMVLALMTVELFGMMGLIGIKLSA
  VPVVILIASVGIGVEFTVHVALAFLTAIGDKNRRAVLALEHMFAPVLDGAVSTLLGVLML
  AGSEFDFIVRYFFAVLAILTILGVLNGLVLLPVLLSFFGPYPEVSPANGLNRLPTPSPEP
  PPSVVRFAMPPGHTHSGSDSSDSEYSSQTTVSGLSEELRHYEAQQGAGGPAHQVIVEATE
  NPVFAHSTVVHPESRHHPPSNPRQQPHLDSGSLPPGRQGQQPRRDPPREGLWPPPYRPRR
  DAFEISTEGHSGPSNRARWGPRGARSHNPRNPASTAMGSSVPGYCQPITTVTASASVTVA
  VHPPPVPGPGRNPRGGLCPGYPETDHGLFEDPHVPFHVRCERRDSKVEVIELQDVECEER
  PRGSSSN
• Function: Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis.
• Tissue Specificity: In the adult, expressed in brain, lung, liver, heart, placenta, skeletal muscle, pancreas and kidney. Expressed in tumor cells but not in normal skin.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Hedgehog sig.ling pathway (hsa04340)
  Axon guidance (hsa04360)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Basal cell carcinoma (hsa05217)
• Reactome Pathway:
  Hedgehog 'off' state (R-HSA-5610787)
  Ligand-receptor interactions (R-HSA-5632681)
  Hedgehog 'on' state (R-HSA-5632684)
  Activation of SMO (R-HSA-5635838)
  Class B/2 (Secretin family receptors) (R-HSA-373080)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Basal cell neoplasm	DIS37IXW	Definitive	Biomarker	[1]
Basal cell nevus syndrome	DIST8BC2	Definitive	Autosomal dominant	[2]
Hereditary hemochromatosis	DISVG5MT	Definitive	Genetic Variation	[3]
Holoprosencephaly 7	DISU3FEX	Definitive	Autosomal dominant	[4]
Rhabdomyosarcoma	DISNR7MS	Definitive	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[6]
Anterior segment dysgenesis 7	DISP6CEE	Strong	Biomarker	[7]
Anxiety	DISIJDBA	Strong	Genetic Variation	[8]
Basal cell carcinoma	DIS7PYN3	Strong	Genetic Variation	[9]
Brachydactyly	DIS2533F	Strong	Genetic Variation	[10]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[11]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[14]
HIV infectious disease	DISO97HC	Strong	Biomarker	[15]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[16]
Oculodentodigital dysplasia	DISSWR9C	Strong	GermlineCausalMutation	[17]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[13]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[18]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[19]
Retinopathy	DISB4B0F	Strong	Biomarker	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[21]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Biomarker	[22]
Wilms tumor	DISB6T16	Strong	Genetic Variation	[23]
Asthma	DISW9QNS	moderate	Biomarker	[24]
Brain cancer	DISBKFB7	moderate	Biomarker	[25]
Isolated cleft lip	DIS2O2JV	moderate	Genetic Variation	[26]
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[27]
Megalencephaly	DISYW5SV	moderate	Genetic Variation	[28]
Melanocytic nevus	DISYS32D	moderate	Genetic Variation	[29]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	CausalMutation	[30]
Carcinoma	DISH9F1N	Limited	Altered Expression	[31]
Holoprosencephaly	DISR35EC	Limited	Autosomal dominant	[32]
Rieger anomaly	DISNBLZ5	Limited	Genetic Variation	[7]

21 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein patched homolog 1 (PTCH1).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein patched homolog 1 (PTCH1).	[34]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein patched homolog 1 (PTCH1).	[35]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein patched homolog 1 (PTCH1).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein patched homolog 1 (PTCH1).	[38]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein patched homolog 1 (PTCH1).	[39]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein patched homolog 1 (PTCH1).	[40]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Protein patched homolog 1 (PTCH1).	[41]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Protein patched homolog 1 (PTCH1).	[35]
Azathioprine	DMMZSXQ	Approved	Azathioprine affects the mutagenesis of Protein patched homolog 1 (PTCH1).	[42]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Protein patched homolog 1 (PTCH1).	[43]
Gemcitabine	DMSE3I7	Approved	Gemcitabine affects the expression of Protein patched homolog 1 (PTCH1).	[44]
Vismodegib	DM5IXKQ	Approved	Vismodegib decreases the expression of Protein patched homolog 1 (PTCH1).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein patched homolog 1 (PTCH1).	[46]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Protein patched homolog 1 (PTCH1).	[47]
APR-246	DMNFADH	Phase 2	APR-246 decreases the expression of Protein patched homolog 1 (PTCH1).	[48]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein patched homolog 1 (PTCH1).	[50]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein patched homolog 1 (PTCH1).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein patched homolog 1 (PTCH1).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein patched homolog 1 (PTCH1).	[53]
CYCLOPAMINE	DMEM2SW	Investigative	CYCLOPAMINE decreases the expression of Protein patched homolog 1 (PTCH1).	[54]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein patched homolog 1 (PTCH1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein patched homolog 1 (PTCH1).	[49]

References

• [1] Ultraviolet and ionizing radiation enhance the growth of BCCs and trichoblastomas in patched heterozygous knockout mice.Nat Med. 1999 Nov;5(11):1285-91. doi: 10.1038/15242.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Expression profile of sonic hedgehog signaling-related molecules in basal cell carcinoma.PLoS One. 2019 Nov 22;14(11):e0225511. doi: 10.1371/journal.pone.0225511. eCollection 2019.
• [4] PTCH mutations in four Brazilian patients with holoprosencephaly and in one with holoprosencephaly-like features and normal MRI. Am J Med Genet A. 2006 Dec 1;140(23):2584-6. doi: 10.1002/ajmg.a.31369.
• [5] Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened.Front Genet. 2019 Jun 12;10:556. doi: 10.3389/fgene.2019.00556. eCollection 2019.
• [6] Aggressive variants of papillary thyroid microcarcinoma are associated with high-risk features, but not decreased survival.Surgery. 2020 Jan;167(1):19-27. doi: 10.1016/j.surg.2019.03.030. Epub 2019 Oct 16.
• [7] Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.Genome Res. 2016 Apr;26(4):474-85. doi: 10.1101/gr.196048.115. Epub 2016 Feb 18.
• [8] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [9] PTCH1 and SMO gene alterations in keratocystic odontogenic tumors.J Dent Res. 2008 Jun;87(6):575-9. doi: 10.1177/154405910808700616.
• [10] A girl with deletion 9q22.1-q22.32 including the PTCH and ROR2 genes identified by genome-wide array-CGH.Am J Med Genet A. 2007 Aug 15;143A(16):1885-9. doi: 10.1002/ajmg.a.31845.
• [11] A rapid and sensitive protocol for competitive reverse transcriptase (cRT) PCR analysis of cellular genes.Brain Pathol. 1998 Jan;8(1):13-8. doi: 10.1111/j.1750-3639.1998.tb00129.x.
• [12] Mutation of the PTCH1 gene predicts recurrence of breast cancer.Sci Rep. 2019 Nov 8;9(1):16359. doi: 10.1038/s41598-019-52617-4.
• [13] The Effect of PTCH1 on Ovarian Cancer Cell Proliferation and Apoptosis.Cancer Biother Radiopharm. 2019 Mar;34(2):103-109. doi: 10.1089/cbr.2018.2626. Epub 2018 Dec 6.
• [14] Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression. Oncotarget. 2016 Nov 29;7(48):78226-78241. doi: 10.18632/oncotarget.12909.
• [15] Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment.Biochem Biophys Res Commun. 2003 Aug 8;307(4):1029-37. doi: 10.1016/s0006-291x(03)01292-0.
• [16] Contributions of PTCH gene variants to isolated cleft lip and palate.Cleft Palate Craniofac J. 2006 Jan;43(1):21-9. doi: 10.1597/04-169r.1.
• [17] Nevoid basal cell carcinoma syndrome (Gorlin syndrome).Orphanet J Rare Dis. 2008 Nov 25;3:32. doi: 10.1186/1750-1172-3-32.
• [18] Combination of hedgehog signaling blockage and chemotherapy leads to tumor reduction in pancreatic adenocarcinomas.Pancreas. 2012 Mar;41(2):222-9. doi: 10.1097/MPA.0b013e31822896dd.
• [19] Protective role of 17 -estradiol on medulloblastoma development in Patched 1 heterozygous mice.Int J Cancer. 2010 Dec 15;127(12):2749-57. doi: 10.1002/ijc.25293.
• [20] Functional rescue of REP1 following treatment with PTC124 and novel derivative PTC-414 in human choroideremia fibroblasts and the nonsense-mediated zebrafish model.Hum Mol Genet. 2016 Aug 15;25(16):3416-3431. doi: 10.1093/hmg/ddw184. Epub 2016 Jun 21.
• [21] Genetic Mutations Underlying Phenotypic Plasticity in Basosquamous Carcinoma.J Invest Dermatol. 2019 Nov;139(11):2263-2271.e5. doi: 10.1016/j.jid.2019.03.1163. Epub 2019 Jun 15.
• [22] The role of the sonic hedgehog signaling pathway in early brain injury after experimental subarachnoid hemorrhage in rats.Neurosci Lett. 2013 Sep 27;552:81-6. doi: 10.1016/j.neulet.2013.07.042. Epub 2013 Aug 7.
• [23] Wilms Tumor Associated With the 9q22.3 Microdeletion Syndrome: 2 New Case Reports and a Review of The Literature.J Pediatr Hematol Oncol. 2019 Nov;41(8):e517-e520. doi: 10.1097/MPH.0000000000001322.
• [24] Importance of hedgehog interacting protein and other lung function genes in asthma.J Allergy Clin Immunol. 2011 Jun;127(6):1457-65. doi: 10.1016/j.jaci.2011.01.056. Epub 2011 Mar 12.
• [25] Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.Cancer Res. 1998 May 1;58(9):1798-803.
• [26] A novel PTCH1 mutation underlies nonsyndromic cleft lip and/or palate in a Han Chinese family.Oral Dis. 2018 Oct;24(7):1318-1325. doi: 10.1111/odi.12915. Epub 2018 Jul 9.
• [27] PTCH1 duplication in a family with microcephaly and mild developmental delay.Eur J Hum Genet. 2009 Feb;17(2):267-71. doi: 10.1038/ejhg.2008.176. Epub 2008 Oct 1.
• [28] Co-occurrence of mutations in FOXP1 and PTCH1 in a girl with extreme megalencephaly, callosal dysgenesis and profound intellectual disability.J Hum Genet. 2018 Nov;63(11):1189-1193. doi: 10.1038/s10038-018-0508-x. Epub 2018 Sep 4.
• [29] The sebaceous nevus: a nevus with deletions of the PTCH gene.Cancer Res. 1999 Apr 15;59(8):1834-6.
• [30] Manifestations of Gorlin-Goltz syndrome.Dan Med J. 2014 May;61(5):A4829.
• [31] Aberrant expression of Sonic hedgehog signaling in Peutz-Jeghers syndrome.Hum Pathol. 2016 Apr;50:153-61. doi: 10.1016/j.humpath.2015.09.044. Epub 2015 Dec 29.
• [32] Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. Hum Genet. 2002 Apr;110(4):297-301. doi: 10.1007/s00439-002-0695-5. Epub 2002 Mar 2.
• [33] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [34] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [35] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [36] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [37] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [38] Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription via DNA damage accumulation. PLoS One. 2013 Jul 8;8(7):e69466. doi: 10.1371/journal.pone.0069466. Print 2013.
• [39] Combined targeting of histone deacetylases and hedgehog signaling enhances cytoxicity in pancreatic cancer. Cancer Biol Ther. 2009 Jul;8(14):1328-39. doi: 10.4161/cbt.8.14.8633. Epub 2009 Jul 6.
• [40] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [41] Down-regulation of Sonic hedgehog signaling pathway activity is involved in 5-fluorouracil-induced apoptosis and motility inhibition in Hep3B cells. Acta Biochim Biophys Sin (Shanghai). 2008 Sep;40(9):819-29.
• [42] PTCH mutations in basal cell carcinomas from azathioprine-treated organ transplant recipients. Br J Cancer. 2008 Oct 21;99(8):1276-84. doi: 10.1038/sj.bjc.6604665.
• [43] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [44] A fine-needle aspirate-based vulnerability assay identifies polo-like kinase 1 as a mediator of gemcitabine resistance in pancreatic cancer. Mol Cancer Ther. 2010 Feb;9(2):311-8. doi: 10.1158/1535-7163.MCT-09-0693. Epub 2010 Jan 26.
• [45] Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. PLoS One. 2011;6(11):e27306. doi: 10.1371/journal.pone.0027306. Epub 2011 Nov 8.
• [46] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [47] Differential regulation of proliferation, cell cycle control and gene expression in cultured human aortic and pulmonary artery endothelial cells by resveratrol. Int J Mol Med. 2010 Nov;26(5):743-9.
• [48] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [49] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [50] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [51] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [52] Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. Hum Mol Genet. 2012 Sep 15;21(18):4104-14. doi: 10.1093/hmg/dds239. Epub 2012 Jun 20.
• [53] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [54] Mono-2-ethyhexyl phthalate advancing the progression of prostate cancer through activating the hedgehog pathway in LNCaP cells. Toxicol In Vitro. 2016 Apr;32:86-91. doi: 10.1016/j.tiv.2015.12.012. Epub 2015 Dec 19.