Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE7JLNM)

• DOT Name: Spondin-2 (SPON2)
• Synonyms: Differentially expressed in cancerous and non-cancerous lung cells 1; DIL-1; Mindin
• Gene Name: SPON2
• Related Disease:
  Metabolic disorder
  Adenocarcinoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Cardiovascular disease
  Classic Hodgkin lymphoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Hepatocellular carcinoma
  Huntington disease
  Lung carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Prostate carcinoma
  Prostate neoplasm
  Laryngeal squamous cell carcinoma
  Non-insulin dependent diabetes
  Prostate cancer
• UniProt ID: SPON2_HUMAN
• PDB ID: 3D34
• Pfam ID: PF06468 ; PF19028
• Sequence:
  MENPSPAAALGKALCALLLATLGAAGQPLGGESICSARALAKYSITFTGKWSQTAFPKQY
  PLFRPPAQWSSLLGAAHSSDYSMWRKNQYVSNGLRDFAERGEAWALMKEIEAAGEALQSV
  HAVFSAPAVPSGTGQTSAELEVQRRHSLVSFVVRIVPSPDWFVGVDSLDLCDGDRWREQA
  ALDLYPYDAGTDSGFTFSSPNFATIPQDTVTEITSSSPSHPANSFYYPRLKALPPIARVT
  LVRLRQSPRAFIPPAPVLPSRDNEIVDSASVPETPLDCEVSLWSSWGLCGGHCGRLGTKS
  RTRYVRVQPANNGSPCPELEEEAECVPDNCV
• Function: Cell adhesion protein that promotes adhesion and outgrowth of hippocampal embryonic neurons. Binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis of bacteria. Essential in the initiation of the innate immune response and represents a unique pattern-recognition molecule in the ECM for microbial pathogens. Binds bacterial lipopolysaccharide (LPS).
• Tissue Specificity: Expressed in normal lung tissue but not in lung carcinoma cell lines.
• Reactome Pathway:
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Defective B3GALTL causes PpS (R-HSA-5083635)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[5]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[8]
Huntington disease	DISQPLA4	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[11]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[12]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[13]
Prostate cancer	DISF190Y	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Spondin-2 (SPON2) affects the response to substance of Mitoxantrone.	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Spondin-2 (SPON2).	[14]

18 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 Spondin-2 (SPON2).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spondin-2 (SPON2).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Spondin-2 (SPON2).	[17]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Spondin-2 (SPON2).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Spondin-2 (SPON2).	[19]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Spondin-2 (SPON2).	[20]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Spondin-2 (SPON2).	[21]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Spondin-2 (SPON2).	[22]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Spondin-2 (SPON2).	[23]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Spondin-2 (SPON2).	[24]
ACYLINE	DM9GRTK	Phase 2	ACYLINE decreases the expression of Spondin-2 (SPON2).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Spondin-2 (SPON2).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Spondin-2 (SPON2).	[27]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Spondin-2 (SPON2).	[28]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Spondin-2 (SPON2).	[29]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Spondin-2 (SPON2).	[26]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Spondin-2 (SPON2).	[30]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Spondin-2 (SPON2).	[31]

References

• [1] Mindin regulates vascular smooth muscle cell phenotype and prevents neointima formation.Clin Sci (Lond). 2015 Jul;129(2):129-45. doi: 10.1042/CS20140679.
• [2] Spondin2 is a new prognostic biomarker for lung adenocarcinoma.Oncotarget. 2017 Jul 26;8(35):59324-59332. doi: 10.18632/oncotarget.19577. eCollection 2017 Aug 29.
• [3] Spondin-2 is a novel diagnostic biomarker for laryngeal squamous cell carcinoma.Pathol Res Pract. 2019 Feb;215(2):286-291. doi: 10.1016/j.prp.2018.11.017. Epub 2018 Nov 29.
• [4] 'Blow my mind(in)' - mindin neutralization for the prevention of atherosclerosis?.Clin Sci (Lond). 2018 Jul 23;132(14):1509-1512. doi: 10.1042/CS20180358. Print 2018 Jul 31.
• [5] Relation of serum spondin-2 levels with cardiac morphology and inflammatory parameters in hemodialysis patients.Int Urol Nephrol. 2018 Nov;50(11):2091-2097. doi: 10.1007/s11255-018-1996-5. Epub 2018 Oct 1.
• [6] Upregulation of spondin-2 predicts poor survival of colorectal carcinoma patients.Oncotarget. 2015 Jun 20;6(17):15095-110. doi: 10.18632/oncotarget.3822.
• [7] The MACC1-SPON2 axis: a new biomarker and therapeutic target in colorectal cancer.Oncogene. 2017 Mar;36(11):1474-1475. doi: 10.1038/onc.2016.322. Epub 2016 Sep 26.
• [8] Upregulation of Spondin-2 protein expression correlates with poor prognosis in hepatocellular carcinoma.J Int Med Res. 2019 Feb;47(2):569-579. doi: 10.1177/0300060518803232. Epub 2018 Oct 14.
• [9] Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display.Genomics. 1999 Oct 1;61(1):5-14. doi: 10.1006/geno.1999.5939.
• [10] Spondin 2 promotes the proliferation, migration and invasion of gastric cancer cells.J Cell Mol Med. 2020 Jan;24(1):98-113. doi: 10.1111/jcmm.14618. Epub 2019 Nov 5.
• [11] Serum BSP, PSADT, and Spondin-2 levels in prostate cancer and the diagnostic significance of their ROC curves in bone metastasis.Eur Rev Med Pharmacol Sci. 2017 Jan;21(1):61-67.
• [12] Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study.Infect Agent Cancer. 2009 Feb 10;4 Suppl 1(Suppl 1):S3. doi: 10.1186/1750-9378-4-S1-S3.
• [13] Mindin: a novel marker for podocyte injury in diabetic nephropathy.Nephrol Dial Transplant. 2011 Jul;26(7):2153-60. doi: 10.1093/ndt/gfq708. Epub 2010 Nov 22.
• [14] 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.
• [15] 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.
• [16] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [17] 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.
• [18] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [19] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [22] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] 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.
• [25] 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.
• [26] Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct immunotoxicants. Arch Toxicol. 2016 Jul;90(7):1685-94. doi: 10.1007/s00204-015-1585-7. Epub 2015 Aug 28.
• [27] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [28] 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.
• [29] 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.
• [30] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [31] 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.
• [32] 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.