Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC8CE0R)

• DOT Name: Tastin (TROAP)
• Synonyms: Trophinin-assisting protein; Trophinin-associated protein
• Gene Name: TROAP
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Hepatocellular carcinoma
  Liver cancer
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Gastric cancer
  Stomach cancer
• UniProt ID: TROAP_HUMAN
• Sequence:
  MTTRQATKDPLLRGVSPTPSKIPVRSQKRTPFPTVTSCAVDQENQDPRRWVQKPPLNIQR
  PLVDSAGPRPKARHQAETSQRLVGISQPRNPLEELRPSPRGQNVGPGPPAQTEAPGTIEF
  VADPAALATILSGEGVKSCHLGRQPSLAKRVLVRGSQGGTTQRVQGVRASAYLAPRTPTH
  RLDPARASCFSRLEGPGPRGRTLCPQRLQALISPSGPSFHPSTRPSFQELRRETAGSSRT
  SVSQASGLLLETPVQPAFSLPKGEREVVTHSDEGGVASLGLAQRVPLRENREMSHTRDSH
  DSHLMPSPAPVAQPLPGHVVPCPSPFGRAQRVPSPGPPTLTSYSVLRRLTVQPKTRFTPM
  PSTPRVQQAQWLRGVSPQSCSEDPALPWEQVAVRLFDQESCIRSLEGSGKPPVATPSGPH
  SNRTPSLQEVKIQRIGILQQLLRQEVEGLVGGQCVPLNGGSSLDMVELQPLLTEISRTLN
  ATEHNSGTSHLPGLLKHSGLPKPCLPEECGEPQPCPPAEPGPPEAFCRSEPEIPEPSLQE
  QLEVPEPYPPAEPRPLESCCRSEPEIPESSRQEQLEVPEPCPPAEPRPLESYCRIEPEIP
  ESSRQEQLEVPEPCPPAEPGPLQPSTQGQSGPPGPCPRVELGASEPCTLEHRSLESSLPP
  CCSQWAPATTSLIFSSQHPLCASPPICSLQSLRPPAGQAGLSNLAPRTLALRERLKSCLT
  AIHCFHEARLDDECAFYTSRAPPSGPTRVCTNPVATLLEWQDALCFIPVGSAAPQGSP
• Function: Could be involved with bystin and trophinin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation.
• Tissue Specificity: Strong expression at implantation sites. Was exclusively localized to the apical side of the syncytiotrophoblast. Also found in macrophages.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[6]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[7]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[7]

16 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 Tastin (TROAP).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tastin (TROAP).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tastin (TROAP).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tastin (TROAP).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tastin (TROAP).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tastin (TROAP).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Tastin (TROAP).	[15]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Tastin (TROAP).	[15]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Tastin (TROAP).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Tastin (TROAP).	[17]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Tastin (TROAP).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tastin (TROAP).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tastin (TROAP).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tastin (TROAP).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tastin (TROAP).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Tastin (TROAP).	[24]

3 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 Tastin (TROAP).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tastin (TROAP).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Tastin (TROAP).	[22]

References

• [1] The Upregulation of Trophinin-Associated Protein (TROAP) Predicts a Poor Prognosis in Hepatocellular Carcinoma.J Cancer. 2019 Jan 29;10(4):957-967. doi: 10.7150/jca.26666. eCollection 2019.
• [2] TROAP Promotes Breast Cancer Proliferation and Metastasis.Biomed Res Int. 2019 May 6;2019:6140951. doi: 10.1155/2019/6140951. eCollection 2019.
• [3] High Trophinin-Associated Protein Expression Is an Independent Predictor of Poor Survival in Liver Cancer.Dig Dis Sci. 2019 Jan;64(1):137-143. doi: 10.1007/s10620-018-5315-x. Epub 2018 Oct 4.
• [4] MicroRNA-519d-3p inhibits cell proliferation and migration by targeting TROAP in colorectal cancer.Biomed Pharmacother. 2018 Sep;105:879-886. doi: 10.1016/j.biopha.2018.04.114. Epub 2018 Jun 18.
• [5] Trophinin-associated protein expression is an independent prognostic biomarker in lung adenocarcinoma.J Thorac Dis. 2019 May;11(5):2043-2050. doi: 10.21037/jtd.2019.04.86.
• [6] TROAP regulates prostate cancer progression via the WNT3/survivin signalling pathways.Oncol Rep. 2019 Feb;41(2):1169-1179. doi: 10.3892/or.2018.6854. Epub 2018 Nov 9.
• [7] Decreased expression of TROAP suppresses cellular proliferation, migration and invasion in gastric cancer.Mol Med Rep. 2018 Sep;18(3):3020-3026. doi: 10.3892/mmr.2018.9230. Epub 2018 Jun 27.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [10] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] 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.
• [14] 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.
• [15] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [16] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [19] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [20] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [21] 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.
• [22] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [23] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [24] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.