Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2GIT0E)

• DOT Name: Protocadherin-10 (PCDH10)
• Gene Name: PCDH10
• Related Disease:
  Autism spectrum disorder
  Gastric neoplasm
  Prostate cancer
  Prostate carcinoma
  Acute lymphocytic leukaemia
  Adult glioblastoma
  Alcohol dependence
  Autism
  B-cell lymphoma
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cervical cancer
  Childhood acute lymphoblastic leukemia
  Cognitive impairment
  Colorectal neoplasm
  Endometrial carcinoma
  Epilepsy
  Glioblastoma multiforme
  Glioma
  Intellectual disability
  Invasive ductal breast carcinoma
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Nasopharyngeal carcinoma
  Non-small-cell lung cancer
  Plasma cell myeloma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Carcinoma of esophagus
  Gastrointestinal stromal tumour
  Cervical carcinoma
  B-cell neoplasm
  Colorectal carcinoma
  Gastric cancer
  Lymphoma
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
  Stomach cancer
  T-cell lymphoma
• UniProt ID: PCD10_HUMAN
• PDB ID: 6VFQ; 6VFW; 6VG4
• Pfam ID: PF00028 ; PF08266 ; PF16492
• Sequence:
  MIVLLLFALLWMVEGVFSQLHYTVQEEQEHGTFVGNIAEDLGLDITKLSARGFQTVPNSR
  TPYLDLNLETGVLYVNEKIDREQICKQSPSCVLHLEVFLENPLELFQVEIEVLDINDNPP
  SFPEPDLTVEISESATPGTRFPLESAFDPDVGTNSLRDYEITPNSYFSLDVQTQGDGNRF
  AELVLEKPLDREQQAVHRYVLTAVDGGGGGGVGEGGGGGGGAGLPPQQQRTGTALLTIRV
  LDSNDNVPAFDQPVYTVSLPENSPPGTLVIQLNATDPDEGQNGEVVYSFSSHISPRAREL
  FGLSPRTGRLEVSGELDYEESPVYQVYVQAKDLGPNAVPAHCKVLVRVLDANDNAPEISF
  STVKEAVSEGAAPGTVVALFSVTDRDSEENGQVQCELLGDVPFRLKSSFKNYYTIVTEAP
  LDREAGDSYTLTVVARDRGEPALSTSKSIQVQVSDVNDNAPRFSQPVYDVYVTENNVPGA
  YIYAVSATDRDEGANAQLAYSILECQIQGMSVFTYVSINSENGYLYALRSFDYEQLKDFS
  FQVEARDAGSPQALAGNATVNILIVDQNDNAPAIVAPLPGRNGTPAREVLPRSAEPGYLL
  TRVAAVDADDGENARLTYSIVRGNEMNLFRMDWRTGELRTARRVPAKRDPQRPYELVIEV
  RDHGQPPLSSTATLVVQLVDGAVEPQGGGGSGGGGSGEHQRPSRSGGGETSLDLTLILII
  ALGSVSFIFLLAMIVLAVRCQKEKKLNIYTCLASDCCLCCCCCGGGGSTCCGRQARARKK
  KLSKSDIMLVQSSNVPSNPAQVPIEESGGFGSHHHNQNYCYQVCLTPESAKTDLMFLKPC
  SPSRSTDTEHNPCGAIVTGYTDQQPDIISNGSILSNETKHQRAELSYLVDRPRRVNSSAF
  QEADIVSSKDSGHGDSEQGDSDHDATNRAQSAGMDLFSNCTEECKALGHSDRCWMPSFVP
  SDGRQAADYRSNLHVPGMDSVPDTEVFETPEAQPGAERSFSTFGKEKALHSTLERKELDG
  LLTNTRAPYKPPYLTRKRIC
• Function: Potential calcium-dependent cell-adhesion protein.
• Tissue Specificity: Moderately expressed in all regions of the brain examined, as well as in testis and ovary, and low expression in all other tissues tested.

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Definitive	Altered Expression	[1]
Gastric neoplasm	DISOKN4Y	Definitive	Biomarker	[2]
Prostate cancer	DISF190Y	Definitive	Posttranslational Modification	[3]
Prostate carcinoma	DISMJPLE	Definitive	Posttranslational Modification	[3]
Acute lymphocytic leukaemia	DISPX75S	Strong	Posttranslational Modification	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[6]
Autism	DISV4V1Z	Strong	Biomarker	[1]
B-cell lymphoma	DISIH1YQ	Strong	Posttranslational Modification	[7]
Bladder cancer	DISUHNM0	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[9]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[9]
Carcinoma	DISH9F1N	Strong	Biomarker	[10]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[11]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Posttranslational Modification	[4]
Cognitive impairment	DISH2ERD	Strong	Genetic Variation	[12]
Colorectal neoplasm	DISR1UCN	Strong	Posttranslational Modification	[13]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[14]
Epilepsy	DISBB28L	Strong	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[15]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[12]
Invasive ductal breast carcinoma	DIS43J58	Strong	Genetic Variation	[9]
leukaemia	DISS7D1V	Strong	Posttranslational Modification	[4]
Leukemia	DISNAKFL	Strong	Posttranslational Modification	[4]
Lung cancer	DISCM4YA	Strong	Altered Expression	[16]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[16]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[17]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[16]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[19]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[8]
Carcinoma of esophagus	DISS6G4D	moderate	Biomarker	[18]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[20]
Cervical carcinoma	DIST4S00	Disputed	Altered Expression	[11]
B-cell neoplasm	DISVY326	Limited	Posttranslational Modification	[21]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[22]
Gastric cancer	DISXGOUK	Limited	Genetic Variation	[23]
Lymphoma	DISN6V4S	Limited	Posttranslational Modification	[21]
Matthew-Wood syndrome	DISA7HR7	Limited	Posttranslational Modification	[24]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[24]
Stomach cancer	DISKIJSX	Limited	Genetic Variation	[23]
T-cell lymphoma	DISSXRTQ	Limited	Posttranslational Modification	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protocadherin-10 (PCDH10).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protocadherin-10 (PCDH10).	[26]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protocadherin-10 (PCDH10).	[27]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protocadherin-10 (PCDH10).	[28]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protocadherin-10 (PCDH10).	[29]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Protocadherin-10 (PCDH10).	[30]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protocadherin-10 (PCDH10).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protocadherin-10 (PCDH10).	[29]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Protocadherin-10 (PCDH10).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protocadherin-10 (PCDH10).	[32]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protocadherin-10 (PCDH10).	[33]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protocadherin-10 (PCDH10).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protocadherin-10 (PCDH10).	[31]

References

• [1] Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.Biol Psychiatry. 2017 Feb 1;81(3):193-202. doi: 10.1016/j.biopsych.2016.06.008. Epub 2016 Jun 16.
• [2] Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer.Gastroenterology. 2009 Feb;136(2):640-51.e1. doi: 10.1053/j.gastro.2008.10.050. Epub 2008 Oct 29.
• [3] Aberrant methylation of PCDH10 predicts worse biochemical recurrence-free survival in patients with prostate cancer after radical prostatectomy.Med Sci Monit. 2014 Aug 3;20:1363-8. doi: 10.12659/MSM.891241.
• [4] Promoter methylation-mediated inactivation of PCDH10 in acute lymphoblastic leukemia contributes to chemotherapy resistance.Genes Chromosomes Cancer. 2011 Dec;50(12):1043-53. doi: 10.1002/gcc.20922. Epub 2011 Aug 24.
• [5] PCDH10 is required for the tumorigenicity of glioblastoma cells.Biochem Biophys Res Commun. 2014 Jan 31;444(1):13-8. doi: 10.1016/j.bbrc.2013.12.138. Epub 2014 Jan 6.
• [6] Cadherins and neuropsychiatric disorders.Brain Res. 2012 Aug 27;1470:130-44. doi: 10.1016/j.brainres.2012.06.020. Epub 2012 Jul 2.
• [7] Clinical significance of PCDH10 promoter methylation in diffuse large B-cell lymphoma.BMC Cancer. 2017 Dec 4;17(1):815. doi: 10.1186/s12885-017-3810-7.
• [8] Clinical and prognostic significance of protocadherin-10 (PCDH10) promoter methylation in bladder cancer.J Int Med Res. 2012;40(6):2117-23. doi: 10.1177/030006051204000609.
• [9] Aberrant promoter methylation of PCDH10 as a potential diagnostic and prognostic biomarker for patients with breast cancer.Oncol Lett. 2018 Oct;16(4):4462-4470. doi: 10.3892/ol.2018.9214. Epub 2018 Jul 25.
• [10] Clinical significance of the methylated cytosine-phosphate-guanine sites of protocadherin-10 promoter for evaluating the prognosis of gastric cancer.J Am Coll Surg. 2014 Nov;219(5):904-13. doi: 10.1016/j.jamcollsurg.2014.06.014. Epub 2014 Jun 26.
• [11] Protocadherin PCDH10, involved in tumor progression, is a frequent and early target of promoter hypermethylation in cervical cancer.Genes Chromosomes Cancer. 2009 Nov;48(11):983-92. doi: 10.1002/gcc.20703.
• [12] Autism spectrum disorder phenotype and intellectual disability in females with epilepsy and PCDH-19 mutations.Epilepsy Behav. 2016 Jul;60:75-80. doi: 10.1016/j.yebeh.2016.04.009. Epub 2016 May 12.
• [13] Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer.J Cancer Res Clin Oncol. 2013 Mar;139(3):485-90. doi: 10.1007/s00432-012-1353-5. Epub 2012 Nov 22.
• [14] A novel wnt regulatory axis in endometrioid endometrial cancer.Cancer Res. 2014 Sep 15;74(18):5103-17. doi: 10.1158/0008-5472.CAN-14-0427. Epub 2014 Aug 1.
• [15] Evaluation of Tumor Regulatory Genes and Apoptotic Pathways in The Cytotoxic Effect of Cytochalasin H on Malignant Human Glioma Cell Line (U87MG).Cell J. 2019 Apr;21(1):62-69. doi: 10.22074/cellj.2019.5948. Epub 2018 Nov 18.
• [16] Protocadherin 10 is frequently downregulated by promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer.Cancer Biomark. 2012-2013;12(1):11-9. doi: 10.3233/CBM-2012-00280.
• [17] PCDH10 is a candidate tumour suppressor gene in medulloblastoma.Childs Nerv Syst. 2011 Aug;27(8):1243-9. doi: 10.1007/s00381-011-1486-x. Epub 2011 May 20.
• [18] High-resolution melting analysis of PCDH10 methylation levels in gastric, colorectal and pancreatic cancers.Neoplasma. 2010;57(3):247-52. doi: 10.4149/neo_2010_03_247.
• [19] PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/-catenin/BCL-9 signaling pathway.Oncol Rep. 2015 Aug;34(2):747-54. doi: 10.3892/or.2015.4056. Epub 2015 Jun 11.
• [20] Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors.Oncotarget. 2016 Nov 15;7(46):75307-75318. doi: 10.18632/oncotarget.12171.
• [21] PCDH10 promoter hypermethylation is frequent in most histologic subtypes of mature lymphoid malignancies and occurs early in lymphomagenesis.Genes Chromosomes Cancer. 2013 Nov;52(11):1030-41. doi: 10.1002/gcc.22098. Epub 2013 Aug 9.
• [22] Epigenetic silencing of protocadherin 10 in colorectal cancer.Oncol Lett. 2017 Apr;13(4):2449-2453. doi: 10.3892/ol.2017.5733. Epub 2017 Feb 13.
• [23] Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for examination of methylated status of protocadherin10 (PCDH10) promoter to predict the prognosis of gastric cancer.Cancer Biomark. 2015;15(5):567-73. doi: 10.3233/CBM-150496.
• [24] High methylation levels of PCDH10 predict poor prognosis in patients with pancreatic ductal adenocarcinoma.BMC Cancer. 2019 May 14;19(1):452. doi: 10.1186/s12885-019-5616-2.
• [25] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [26] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [27] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [28] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [29] 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.
• [30] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [31] 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.
• [32] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [33] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [34] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.