Details of Drug Off-Target (DOT)

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

• DOT Name: Tetraspanin-1 (TSPAN1)
• Synonyms: Tspan-1; Tetraspan NET-1; Tetraspanin TM4-C
• Gene Name: TSPAN1
• Related Disease:
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Cervical Intraepithelial neoplasia
  Cholangiocarcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congenital contractural arachnodactyly
  Cutaneous squamous cell carcinoma
  Dentin dysplasia
  Dentinogenesis imperfecta
  Esophageal cancer
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Herpes simplex infection
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Skin cancer
  Squamous cell carcinoma
  Stomach cancer
  Uterine cervix neoplasm
  Carcinoma
  Gastric adenocarcinoma
  Nasopharyngeal carcinoma
  Pulmonary fibrosis
  Adenocarcinoma
  Pancreatic ductal carcinoma
  Bone osteosarcoma
  Colorectal adenocarcinoma
  Malignant soft tissue neoplasm
  Osteosarcoma
  Sarcoma
• UniProt ID: TSN1_HUMAN
• Pfam ID: PF00335
• Sequence:
  MQCFSFIKTMMILFNLLIFLCGAALLAVGIWVSIDGASFLKIFGPLSSSAMQFVNVGYFL
  IAAGVVVFALGFLGCYGAKTESKCALVTFFFILLLIFIAEVAAAVVALVYTTMAEHFLTL
  LVVPAIKKDYGSQEDFTQVWNTTMKGLKCCGFTNYTDFEDSPYFKENSAFPPFCCNDNVT
  NTANETCTKQKAHDQKVEGCFNQLLYDIRTNAVTVGGVAAGIGGLELAAMIVSMYLYCNL
  Q

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[3]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[4]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Altered Expression	[5]
Cutaneous squamous cell carcinoma	DIS3LXUG	Strong	Biomarker	[8]
Dentin dysplasia	DISCGIX8	Strong	Genetic Variation	[9]
Dentinogenesis imperfecta	DISJLZU4	Strong	Genetic Variation	[9]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[3]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[10]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[13]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Skin cancer	DISTM18U	Strong	Biomarker	[15]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[4]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[10]
Uterine cervix neoplasm	DIS0BYVV	Strong	Altered Expression	[4]
Carcinoma	DISH9F1N	moderate	Altered Expression	[16]
Gastric adenocarcinoma	DISWWLTC	moderate	Biomarker	[17]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[18]
Pulmonary fibrosis	DISQKVLA	moderate	Altered Expression	[19]
Adenocarcinoma	DIS3IHTY	Disputed	Altered Expression	[20]
Pancreatic ductal carcinoma	DIS26F9Q	Disputed	Altered Expression	[21]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[22]
Colorectal adenocarcinoma	DISPQOUB	Limited	Altered Expression	[20]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Biomarker	[23]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[22]
Sarcoma	DISZDG3U	Limited	Biomarker	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tetraspanin-1 (TSPAN1).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tetraspanin-1 (TSPAN1).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tetraspanin-1 (TSPAN1).	[26]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tetraspanin-1 (TSPAN1).	[27]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Tetraspanin-1 (TSPAN1).	[28]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tetraspanin-1 (TSPAN1).	[29]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Tetraspanin-1 (TSPAN1).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tetraspanin-1 (TSPAN1).	[32]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Tetraspanin-1 (TSPAN1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tetraspanin-1 (TSPAN1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Tetraspanin-1 (TSPAN1).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tetraspanin-1 (TSPAN1).	[35]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tetraspanin-1 (TSPAN1).	[36]

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 increases the methylation of Tetraspanin-1 (TSPAN1).	[31]

References

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• [2] Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach.J Cancer Res Clin Oncol. 2011 May;137(5):795-809. doi: 10.1007/s00432-010-0937-1. Epub 2010 Aug 3.
• [3] TSPAN1 upregulates MMP2 to promote pancreatic cancer cell migration and invasion via PLC.Oncol Rep. 2019 Apr;41(4):2117-2125. doi: 10.3892/or.2019.6989. Epub 2019 Jan 30.
• [4] Identification of a new proliferation-associated protein NET-1/C4.8 characteristic for a subset of high-grade cervical intraepithelial neoplasia and cervical carcinomas.Int J Cancer. 2002 Jun 20;99(6):771-5. doi: 10.1002/ijc.10442.
• [5] Tetraspanin 1 promotes epithelial-to-mesenchymal transition and metastasis of cholangiocarcinoma via PI3K/AKT signaling.J Exp Clin Cancer Res. 2018 Dec 4;37(1):300. doi: 10.1186/s13046-018-0969-y.
• [6] Discovery of a diagnostic biomarker for colon cancer through proteomic profiling of small extracellular vesicles.BMC Cancer. 2018 Nov 1;18(1):1058. doi: 10.1186/s12885-018-4952-y.
• [7] MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma.Oncotarget. 2014 Dec 15;5(23):12083-96. doi: 10.18632/oncotarget.2499.
• [8] Inhibition of skin squamous cell carcinoma proliferation and promote apoptosis by dual silencing of NET-1 and survivin.Oncol Rep. 2015 Aug;34(2):811-22. doi: 10.3892/or.2015.4062. Epub 2015 Jun 15.
• [9] Overlapping DSPP mutations cause dentin dysplasia and dentinogenesis imperfecta.J Dent Res. 2008 Dec;87(12):1108-11. doi: 10.1177/154405910808701217.
• [10] TSPAN1 functions as an oncogene in gastric cancer and is downregulated by miR-573.FEBS Lett. 2015 Jul 8;589(15):1988-94. doi: 10.1016/j.febslet.2015.05.044. Epub 2015 Jun 6.
• [11] Midkine promotes tetraspanin-integrin interaction and induces FAK-Stat1alpha pathway contributing to migration/invasiveness of human head and neck squamous cell carcinoma cells.Biochem Biophys Res Commun. 2008 Dec 12;377(2):474-478. doi: 10.1016/j.bbrc.2008.09.138. Epub 2008 Oct 11.
• [12] Inhibition of NET-1 suppresses proliferation and promotes apoptosis of hepatocellular carcinoma cells by activating the PI3K/AKT signaling pathway.Exp Ther Med. 2019 Mar;17(3):2334-2340. doi: 10.3892/etm.2019.7211. Epub 2019 Jan 29.
• [13] A net +1 frameshift permits synthesis of thymidine kinase from a drug-resistant herpes simplex virus mutant.Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5461-5. doi: 10.1073/pnas.91.12.5461.
• [14] Neuroepithelial transforming gene 1 functions as a potential prognostic marker for patients with non-small cell lung cancer.Mol Med Rep. 2015 Nov;12(5):7439-46. doi: 10.3892/mmr.2015.4385. Epub 2015 Sep 29.
• [15] Knockdown of TSPAN1 by RNA silencing and antisense technique inhibits proliferation and infiltration of human skin squamous carcinoma cells.Tumori. 2010 Mar-Apr;96(2):289-95. doi: 10.1177/030089161009600217.
• [16] Silencing Tspan1 inhibits migration and invasion, and induces the apoptosis of human pancreatic cancer cells.Mol Med Rep. 2018 Sep;18(3):3280-3288. doi: 10.3892/mmr.2018.9331. Epub 2018 Jul 27.
• [17] Net1 and Myeov: computationally identified mediators of gastric cancer.Br J Cancer. 2006 Apr 24;94(8):1204-12. doi: 10.1038/sj.bjc.6603054.
• [18] Identification of candidate molecular markers of nasopharyngeal carcinoma by tissue microarray and in situ hybridization.Med Oncol. 2011 Dec;28 Suppl 1:S341-8. doi: 10.1007/s12032-010-9727-5. Epub 2010 Nov 5.
• [19] Tetraspanin 1 as a mediator of fibrosis inhibits EMT process and Smad2/3 and beta-catenin pathway in human pulmonary fibrosis.J Cell Mol Med. 2019 May;23(5):3583-3596. doi: 10.1111/jcmm.14258. Epub 2019 Mar 14.
• [20] TSPAN1 protein expression: a significant prognostic indicator for patients with colorectal adenocarcinoma.World J Gastroenterol. 2009 May 14;15(18):2270-6. doi: 10.3748/wjg.15.2270.
• [21] Screening and validating the core biomarkers in patients with pancreatic ductal adenocarcinoma.Math Biosci Eng. 2019 Nov 6;17(1):910-927. doi: 10.3934/mbe.2020048.
• [22] miR-491-3p suppresses the growth and invasion of osteosarcoma cells by targeting TSPAN1.Mol Med Rep. 2017 Oct;16(4):5568-5574. doi: 10.3892/mmr.2017.7256. Epub 2017 Aug 16.
• [23] Genomic structure of SAS, a member of the transmembrane 4 superfamily amplified in human sarcomas.Genomics. 1995 Jan 20;25(2):501-6. doi: 10.1016/0888-7543(95)80051-m.
• [24] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [25] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [26] Profile of estrogen-responsive genes in an estrogen-specific mammary gland outgrowth model. Mol Reprod Dev. 2009 Aug;76(8):733-50. doi: 10.1002/mrd.21041.
• [27] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [28] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [29] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [30] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [33] 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.
• [34] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [35] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [36] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.