Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH8MC64)

• DOT Name: CD82 antigen (CD82)
• Synonyms: C33 antigen; IA4; Inducible membrane protein R2; Metastasis suppressor Kangai-1; Suppressor of tumorigenicity 6 protein; Tetraspanin-27; Tspan-27; CD antigen CD82
• Gene Name: CD82
• Related Disease:
  Bladder cancer
  Breast neoplasm
  Esophageal cancer
  Melanoma
  Neuroblastoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Acute myelogenous leukaemia
  Adenocarcinoma
  Benign prostatic hyperplasia
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Endometrium neoplasm
  Epithelial neoplasm
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioma
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Liver cancer
  Lung adenocarcinoma
  Nasopharyngeal carcinoma
  Non-small-cell lung cancer
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Plasma cell myeloma
  Rheumatoid arthritis
  Sarcoma
  Squamous cell carcinoma
  Head and neck cancer
  Head and neck carcinoma
  Lung cancer
  Oral cancer
  Lung carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Gastric cancer
  Hepatitis C virus infection
  High blood pressure
  Renal cell carcinoma
  Stomach cancer
• UniProt ID: CD82_HUMAN
• Pfam ID: PF00335
• Sequence:
  MGSACIKVTKYFLFLFNLIFFILGAVILGFGVWILADKSSFISVLQTSSSSLRMGAYVFI
  GVGAVTMLMGFLGCIGAVNEVRCLLGLYFAFLLLILIAQVTAGALFYFNMGKLKQEMGGI
  VTELIRDYNSSREDSLQDAWDYVQAQVKCCGWVSFYNWTDNAELMNRPEVTYPCSCEVKG
  EEDNSLSVRKGFCEAPGNRTQSGNHPEDWPVYQEGCMEKVQAWLQENLGIILGVGVGVAI
  IELLGMVLSICLCRHVHSEDYSKVPKY
• Function: Associates with CD4 or CD8 and delivers costimulatory signals for the TCR/CD3 pathway.
• Tissue Specificity: Lymphoid specific.
• KEGG Pathway: p53 sig.ling pathway (hsa04115)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Definitive	Altered Expression	[2]
Esophageal cancer	DISGB2VN	Definitive	Altered Expression	[3]
Melanoma	DIS1RRCY	Definitive	Biomarker	[4]
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[5]
Urinary bladder cancer	DISDV4T7	Definitive	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[6]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[7]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[10]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[12]
Endometrium neoplasm	DIS6OS2L	Strong	Altered Expression	[13]
Epithelial neoplasm	DIS0T594	Strong	Altered Expression	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Altered Expression	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[17]
leukaemia	DISS7D1V	Strong	Biomarker	[6]
Leukemia	DISNAKFL	Strong	Biomarker	[6]
Liver cancer	DISDE4BI	Strong	Altered Expression	[18]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[19]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Osteoarthritis	DIS05URM	Strong	Biomarker	[22]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[23]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[23]
Pancreatic cancer	DISJC981	Strong	Biomarker	[24]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[25]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[26]
Sarcoma	DISZDG3U	Strong	Altered Expression	[13]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[27]
Head and neck cancer	DISBPSQZ	moderate	Genetic Variation	[28]
Head and neck carcinoma	DISOU1DS	moderate	Genetic Variation	[28]
Lung cancer	DISCM4YA	moderate	Altered Expression	[19]
Oral cancer	DISLD42D	moderate	Biomarker	[29]
Lung carcinoma	DISTR26C	Disputed	Altered Expression	[19]
Endometrial cancer	DISW0LMR	Limited	Altered Expression	[30]
Endometrial carcinoma	DISXR5CY	Limited	Altered Expression	[30]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[31]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[32]
High blood pressure	DISY2OHH	Limited	Biomarker	[33]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[11]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[31]

20 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 CD82 antigen (CD82).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CD82 antigen (CD82).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CD82 antigen (CD82).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CD82 antigen (CD82).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of CD82 antigen (CD82).	[38]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CD82 antigen (CD82).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of CD82 antigen (CD82).	[40]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of CD82 antigen (CD82).	[40]
Marinol	DM70IK5	Approved	Marinol decreases the expression of CD82 antigen (CD82).	[41]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of CD82 antigen (CD82).	[42]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of CD82 antigen (CD82).	[43]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of CD82 antigen (CD82).	[44]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of CD82 antigen (CD82).	[45]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of CD82 antigen (CD82).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CD82 antigen (CD82).	[48]
Terfenadine	DM4KLPT	Withdrawn from market	Terfenadine increases the expression of CD82 antigen (CD82).	[49]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of CD82 antigen (CD82).	[50]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of CD82 antigen (CD82).	[52]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of CD82 antigen (CD82).	[53]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of CD82 antigen (CD82).	[54]

2 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 CD82 antigen (CD82).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of CD82 antigen (CD82).	[51]

References

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• [2] Transcriptional and translational modulation of KAI1 expression in ductal carcinoma of the breast and the prognostic significance.Int J Mol Med. 2009 Feb;23(2):273-8.
• [3] KAI1 metastasis suppressor gene is frequently down-regulated in cervical carcinoma.Am J Pathol. 2001 Nov;159(5):1629-34. doi: 10.1016/s0002-9440(10)63009-x.
• [4] CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by mediating U2AF2 ubiquitination and degradation.Oncogene. 2016 Sep 22;35(38):5056-5069. doi: 10.1038/onc.2016.67. Epub 2016 Apr 4.
• [5] Frequent low level expression in Ewing sarcoma family tumors and widespread absence of the metastasis suppressor KAI1/CD82 in neuroblastoma.Pediatr Res. 2002 Aug;52(2):279-85. doi: 10.1203/00006450-200208000-00022.
• [6] CD82 supports survival of childhood acute myeloid leukemia cells via activation of Wnt/-catenin signaling pathway.Pediatr Res. 2019 Jun;85(7):1024-1031. doi: 10.1038/s41390-019-0370-3. Epub 2019 Mar 12.
• [7] Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.Cancer Res. 1996 Apr 15;56(8):1751-5.
• [8] KAI1/CD82 gene expression in benign prostatic hyperplasia and late-stage prostate cancer in Chinese.Asian J Androl. 2000 Sep;2(3):221-4.
• [9] Expression of KAI1/CD82 in distant metastases from estrogen receptor-negative breast cancer.Cancer Sci. 2009 Sep;100(9):1767-71. doi: 10.1111/j.1349-7006.2009.01231.x. Epub 2009 May 27.
• [10] Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis.Genet Mol Res. 2015 Dec 16;14(4):17059-67. doi: 10.4238/2015.December.16.6.
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• [15] CD82/KAI1 inhibits invasion and metastasis of esophageal squamous cell carcinoma via TGF-1.Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5928-5937. doi: 10.26355/eurrev_201809_15922.
• [16] Characteristics of the expression of KAI1/CD82 and PDGFR and their impact on glioma progression.Folia Neuropathol. 2016;54(3):241-248. doi: 10.5114/fn.2016.62554.
• [17] Interaction of transforming growth factor--Smads/microRNA-362-3p/CD82 mediated by M2 macrophages promotes the process of epithelial-mesenchymal transition in hepatocellular carcinoma cells.Cancer Sci. 2019 Aug;110(8):2507-2519. doi: 10.1111/cas.14101. Epub 2019 Jul 9.
• [18] KAI1 gene suppresses invasion and metastasis of hepatocellular carcinoma MHCC97-H cells in vitro and in animal models.Liver Int. 2008 Jan;28(1):132-9. doi: 10.1111/j.1478-3231.2007.01620.x. Epub 2007 Nov 19.
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• [20] KAI1 overexpression promotes apoptosis and inhibits proliferation, cell cycle, migration, and invasion in nasopharyngeal carcinoma cells.Am J Otolaryngol. 2017 Sep-Oct;38(5):511-517. doi: 10.1016/j.amjoto.2016.09.011. Epub 2016 Sep 28.
• [21] Expressions of KAI1 and E-cadherin in nonsmall cell lung cancer and their correlation with vasculogenic mimicry.Medicine (Baltimore). 2018 Oct;97(40):e12293. doi: 10.1097/MD.0000000000012293.
• [22] Tetraspanin CD82 affects migration, attachment and invasion of rheumatoid arthritis synovial fibroblasts.Ann Rheum Dis. 2018 Nov;77(11):1619-1626. doi: 10.1136/annrheumdis-2018-212954. Epub 2018 Jul 6.
• [23] Alternative splicing of KAI1 abrogates its tumor-suppressive effects on integrin v3-mediated ovarian cancer biology.Cell Signal. 2015 Mar;27(3):652-62. doi: 10.1016/j.cellsig.2014.11.028. Epub 2014 Nov 27.
• [24] Combined Exosomal GPC1, CD82, and Serum CA19-9 as Multiplex Targets: A Specific, Sensitive, and Reproducible Detection Panel for the Diagnosis of Pancreatic Cancer.Mol Cancer Res. 2020 Feb;18(2):300-310. doi: 10.1158/1541-7786.MCR-19-0588. Epub 2019 Oct 29.
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• [26] Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissection.Arthritis Rheum. 2007 Apr;56(4):1094-105. doi: 10.1002/art.22450.
• [27] Gene therapy for head and neck squamous cell carcinoma using KITENIN (KAI1 COOH-Terminal Interacting Tetraspanin)-antisense therapy.Yonsei Med J. 2011 May;52(3):463-8. doi: 10.3349/ymj.2011.52.3.463.
• [28] Lack of germ line changes in KISS1 and KAI1 genes in sporadic head and neck cancer patients of Pakistani origin.Asian Pac J Cancer Prev. 2011;12(10):2767-71.
• [29] Overexpression of KAI1/CD82 suppresses invitro cell growth, migration, invasion and xenograft growth in oral cancer.Mol Med Rep. 2017 Apr;15(4):1527-1532. doi: 10.3892/mmr.2017.6186. Epub 2017 Feb 9.
• [30] The relationships between the immunoexpression of KAI1, MMP-2, MMP-9 and steroid receptors expression in endometrial cancer.Folia Histochem Cytobiol. 2014;52(3):187-94. doi: 10.5603/FHC.2014.0022.
• [31] Nuclear Drosha enhances cell invasion via an EGFR-ERK1/2-MMP7 signaling pathway induced by dysregulated miRNA-622/197 and their targets LAMC2 and CD82 in gastric cancer.Cell Death Dis. 2017 Mar 2;8(3):e2642. doi: 10.1038/cddis.2017.5.
• [32] KAI1, a prostate metastasis suppressor: prediction of solvated structure and interactions with binding partners; integrins, cadherins, and cell-surface receptor proteins.Mol Carcinog. 2001 Nov;32(3):139-53. doi: 10.1002/mc.1073.
• [33] Identification of upregulated genes in the thymus of spontaneously hypertensive rats by cDNA representational difference analysis.Blood Press. 1998 Nov;7(5-6):316-23. doi: 10.1080/080370598437196.
• [34] 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.
• [35] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [36] 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.
• [37] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [38] CD82 gene suppression in endometrial stromal cells leads to increase of the cell invasiveness in the endometriotic milieu. J Mol Endocrinol. 2011 Aug 31;47(2):195-208. doi: 10.1530/JME-10-0165. Print 2011 Oct.
• [39] 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.
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• [41] 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.
• [42] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [43] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [44] Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
• [45] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [46] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [47] 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.
• [48] 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.
• [49] Selective inhibitors of CYP2J2 related to terfenadine exhibit strong activity against human cancers in vitro and in vivo. J Pharmacol Exp Ther. 2009 Jun;329(3):908-18. doi: 10.1124/jpet.109.152017. Epub 2009 Mar 16.
• [50] Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
• [51] 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.
• [52] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [53] 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.
• [54] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.