Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1F68WQ)

• DOT Name: Tetraspanin-8 (TSPAN8)
• Synonyms: Tspan-8; Transmembrane 4 superfamily member 3; Tumor-associated antigen CO-029
• Gene Name: TSPAN8
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Adult glioblastoma
  Advanced cancer
  Atrial fibrillation
  Attention deficit hyperactivity disorder
  Breast cancer
  Breast carcinoma
  Bronchopulmonary dysplasia
  Carcinoma
  Colon cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Malignant glioma
  Melanoma
  Mental disorder
  Metastatic malignant neoplasm
  Neuroblastoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Type-1/2 diabetes
  Bipolar disorder
  Colon carcinoma
  Gastric cancer
  Schizophrenia
  Stomach cancer
  Neoplasm
  Adult respiratory distress syndrome
  Colorectal carcinoma
  Melanocytic nevus
  Nasopharyngeal carcinoma
  Neoplasm of esophagus
  Pancreatic cancer
• UniProt ID: TSN8_HUMAN
• Pfam ID: PF00335
• Sequence:
  MAGVSACIKYSMFTFNFLFWLCGILILALAIWVRVSNDSQAIFGSEDVGSSSYVAVDILI
  AVGAIIMILGFLGCCGAIKESRCMLLLFFIGLLLILLLQVATGILGAVFKSKSDRIVNET
  LYENTKLLSATGESEKQFQEAIIVFQEEFKCCGLVNGAADWGNNFQHYPELCACLDKQRP
  CQSYNGKQVYKETCISFIKDFLAKNLIIVIGISFGLAVIEILGLVFSMVLYCQIGNK
• Tissue Specificity: Gastric, colon, rectal, and pancreatic carcinomas.

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Definitive	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[4]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Genetic Variation	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[12]
Lung carcinoma	DISTR26C	Strong	Biomarker	[12]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Mental disorder	DIS3J5R8	Strong	Altered Expression	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[6]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[13]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[12]
Obesity	DIS47Y1K	Strong	Genetic Variation	[15]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[4]
Bipolar disorder	DISAM7J2	moderate	Altered Expression	[13]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[9]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[16]
Schizophrenia	DISSRV2N	moderate	Biomarker	[7]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[16]
Neoplasm	DISZKGEW	Disputed	Biomarker	[17]
Adult respiratory distress syndrome	DISIJV47	Limited	Biomarker	[18]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[19]
Melanocytic nevus	DISYS32D	Limited	Altered Expression	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[17]
Neoplasm of esophagus	DISOLKAQ	Limited	Altered Expression	[21]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[22]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Tetraspanin-8 (TSPAN8) affects the response to substance of Topotecan.	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Tetraspanin-8 (TSPAN8).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tetraspanin-8 (TSPAN8).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tetraspanin-8 (TSPAN8).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tetraspanin-8 (TSPAN8).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tetraspanin-8 (TSPAN8).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tetraspanin-8 (TSPAN8).	[26]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tetraspanin-8 (TSPAN8).	[27]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tetraspanin-8 (TSPAN8).	[28]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tetraspanin-8 (TSPAN8).	[29]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Tetraspanin-8 (TSPAN8).	[30]
ACYLINE	DM9GRTK	Phase 2	ACYLINE increases the expression of Tetraspanin-8 (TSPAN8).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tetraspanin-8 (TSPAN8).	[33]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tetraspanin-8 (TSPAN8).	[34]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Tetraspanin-8 (TSPAN8).	[36]

References

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• [2] Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression.Biochem Biophys Res Commun. 2015 Mar 13;458(3):476-482. doi: 10.1016/j.bbrc.2015.01.128. Epub 2015 Feb 11.
• [3] TSPAN8 promotes cancer cell stemness via activation of sonic Hedgehog signaling.Nat Commun. 2019 Jun 28;10(1):2863. doi: 10.1038/s41467-019-10739-3.
• [4] Genetic susceptibility for ischemic infarction and arteriolosclerosis based on neuropathologic evaluations.Cerebrovasc Dis. 2013;36(3):181-188. doi: 10.1159/000352054. Epub 2013 Oct 12.
• [5] Bipolar disorder risk alleles in adult ADHD patients.Genes Brain Behav. 2011 Jun;10(4):418-23. doi: 10.1111/j.1601-183X.2011.00680.x. Epub 2011 Feb 18.
• [6] Tspan8 is expressed in breast cancer and regulates E-cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles.J Pathol. 2019 Aug;248(4):421-437. doi: 10.1002/path.5281. Epub 2019 Jun 18.
• [7] Functional variants of TSPAN8 are associated with bipolar disorder and schizophrenia.Am J Med Genet B Neuropsychiatr Genet. 2010 Jun 5;153B(4):967-72. doi: 10.1002/ajmg.b.31057.
• [8] E-cadherin/p120-catenin and tetraspanin Co-029 cooperate for cell motility control in human colon carcinoma.Cancer Res. 2010 Oct 1;70(19):7674-83. doi: 10.1158/0008-5472.CAN-09-4482. Epub 2010 Sep 21.
• [9] Ultrasensitive NIR-SERRS Probes with Multiplexed Ratiometric Quantification for In Vivo Antibody Leads Validation.Adv Healthc Mater. 2018 Feb;7(4). doi: 10.1002/adhm.201700870. Epub 2017 Dec 1.
• [10] Tetraspanin 8-rictor-integrin 3 complex is required for glioma cell migration.Int J Mol Sci. 2015 Mar 9;16(3):5363-74. doi: 10.3390/ijms16035363.
• [11] Tetraspanin 8 mediates AEG-1-induced invasion and metastasis in hepatocellular carcinoma cells.FEBS Lett. 2016 Aug;590(16):2700-8. doi: 10.1002/1873-3468.12268. Epub 2016 Jul 21.
• [12] Overexpression of TSPAN8 Promotes Tumor Cell Viability and Proliferation in Nonsmall Cell Lung Cancer.Cancer Biother Radiopharm. 2016 Dec;31(10):353-359. doi: 10.1089/cbr.2016.2108.
• [13] The regulation of tetraspanin 8 gene expression-A potential new mechanism in the pathogenesis of bipolar disorder.Am J Med Genet B Neuropsychiatr Genet. 2017 Oct;174(7):740-750. doi: 10.1002/ajmg.b.32571. Epub 2017 Aug 4.
• [14] Blood-based analysis of type-2 diabetes mellitus susceptibility genes identifies specific transcript variants with deregulated expression and association with disease risk.Sci Rep. 2019 Feb 6;9(1):1512. doi: 10.1038/s41598-018-37856-1.
• [15] Obesity and diabetes genetic variants associated with gestational weight gain.Am J Obstet Gynecol. 2010 Sep;203(3):283.e1-17. doi: 10.1016/j.ajog.2010.06.069.
• [16] Quantitative proteomics analysis of the role of tetraspanin-8 in the drug resistance of gastric cancer.Int J Oncol. 2018 Feb;52(2):473-484. doi: 10.3892/ijo.2017.4231. Epub 2017 Dec 19.
• [17] TSPAN8 serves as a prognostic marker involving Akt/MAPK pathway in nasopharyngeal carcinoma.Ann Transl Med. 2019 Sep;7(18):470. doi: 10.21037/atm.2019.08.02.
• [18] MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome.BMC Med Genomics. 2014 Jul 28;7:46. doi: 10.1186/1755-8794-7-46.
• [19] TSPAN8 promotes colorectal cancer cell growth and migration in LSD1-dependent manner.Life Sci. 2020 Jan 15;241:117114. doi: 10.1016/j.lfs.2019.117114. Epub 2019 Nov 29.
• [20] Tspan8--catenin positive feedback loop promotes melanoma invasion.Oncogene. 2019 May;38(20):3781-3793. doi: 10.1038/s41388-019-0691-z. Epub 2019 Jan 24.
• [21] TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression.Clin Exp Metastasis. 2008;25(5):537-48. doi: 10.1007/s10585-008-9168-0. Epub 2008 Mar 26.
• [22] The Pancreatic Cancer-Initiating Cell Marker CD44v6 Affects Transcription, Translation, and Signaling: Consequences for Exosome Composition and Delivery.J Oncol. 2019 Aug 7;2019:3516973. doi: 10.1155/2019/3516973. eCollection 2019.
• [23] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [24] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [25] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [26] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [27] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [28] Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles. Fertil Steril. 2008 Dec;90(6):2152-64.
• [29] 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.
• [30] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [31] Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
• [32] 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.
• [33] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [34] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [35] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [36] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [37] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.