Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSRC874)

DOT Name	Lumican (LUM)
Synonyms	Keratan sulfate proteoglycan lumican; KSPG lumican
Gene Name	LUM
Related Disease	Adenocarcinoma ( ) Lung adenocarcinoma ( ) Pulmonary disease ( ) Advanced cancer ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Bladder cancer ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma ( ) Cardiac failure ( ) Colorectal carcinoma ( ) Congestive heart failure ( ) Epithelial ovarian cancer ( ) facioscapulohumeral muscular dystrophy ( ) Hepatitis C virus infection ( ) Isovaleric acidemia ( ) Liver cirrhosis ( ) Lung cancer ( ) Lung carcinoma ( ) Osteoarthritis ( ) Osteosarcoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Pancreatic ductal carcinoma ( ) Systemic lupus erythematosus ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Gastric cancer ( ) Hypertrophic cardiomyopathy ( ) Metastatic malignant neoplasm ( ) Obesity ( ) Stomach cancer ( ) Melanoma ( ) Colon cancer ( ) Colon carcinoma ( ) Coronary heart disease ( ) Cystic fibrosis ( ) Ehlers-Danlos syndrome, classic type, 1 ( ) Glioma ( ) Matthew-Wood syndrome ( ) Myopia ( ) Pancreatic adenocarcinoma ( ) Pancreatic cancer ( ) Squamous cell carcinoma ( )
UniProt ID	LUM_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF13516 ; PF13855 ; PF01462
Sequence	MSLSAFTLFLALIGGTSGQYYDYDFPLSIYGQSSPNCAPECNCPESYPSAMYCDELKLKS VPMVPPGIKYLYLRNNQIDHIDEKAFENVTDLQWLILDHNLLENSKIKGRVFSKLKQLKK LHINHNNLTESVGPLPKSLEDLQLTHNKITKLGSFEGLVNLTFIHLQHNRLKEDAVSAAF KGLKSLEYLDLSFNQIARLPSGLPVSLLTLYLDNNKISNIPDEYFKRFNALQYLRLSHNE LADSGIPGNSFNVSSLVELDLSYNKLKNIPTVNENLENYYLEVNQLEKFDIKSFCKILGP LSYSKIKHLRLDGNRISETSLPPDMYECLRVANEVTLN
Tissue Specificity	Cornea and other tissues.
KEGG Pathway	Proteoglycans in cancer (hsa05205 )
Reactome Pathway	Keratan sulfate degradation (R-HSA-2022857 ) Integrin cell surface interactions (R-HSA-216083 ) ECM proteoglycans (R-HSA-3000178 ) Defective CHST6 causes MCDC1 (R-HSA-3656225 ) Defective ST3GAL3 causes MCT12 and EIEE15 (R-HSA-3656243 ) Defective B4GALT1 causes B4GALT1-CDG (CDG-2d) (R-HSA-3656244 ) Keratan sulfate biosynthesis (R-HSA-2022854 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adenocarcinoma	DIS3IHTY	Definitive	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[1]
Pulmonary disease	DIS6060I	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Cardiac failure	DISDC067	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[11]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
facioscapulohumeral muscular dystrophy	DISSE0H0	Strong	Biomarker	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[14]
Isovaleric acidemia	DIS3ETX9	Strong	Biomarker	[15]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[18]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[19]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[20]
Hypertrophic cardiomyopathy	DISQG2AI	moderate	Altered Expression	[21]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[22]
Obesity	DIS47Y1K	moderate	Biomarker	[23]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[20]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[24]
Colon cancer	DISVC52G	Limited	Altered Expression	[25]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[25]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[26]
Cystic fibrosis	DIS2OK1Q	Limited	Genetic Variation	[27]
Ehlers-Danlos syndrome, classic type, 1	DIS4BR9L	Limited	Biomarker	[28]
Glioma	DIS5RPEH	Limited	Biomarker	[29]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[3]
Myopia	DISK5S60	Limited	Biomarker	[30]
Pancreatic adenocarcinoma	DISKHX7S	Limited	Biomarker	[3]
Pancreatic cancer	DISJC981	Limited	Biomarker	[3]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[11]
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⏷ Show the Full List of 47 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Lumican (LUM) decreases the response to substance of Cisplatin.	[52]
Methotrexate	DM2TEOL	Approved	Lumican (LUM) decreases the response to substance of Methotrexate.	[52]
Paclitaxel	DMLB81S	Approved	Lumican (LUM) decreases the response to substance of Paclitaxel.	[52]
Topotecan	DMP6G8T	Approved	Lumican (LUM) decreases the response to substance of Topotecan.	[52]
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2 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 Lumican (LUM).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lumican (LUM).	[48]
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19 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 Lumican (LUM).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lumican (LUM).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lumican (LUM).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lumican (LUM).	[35]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Lumican (LUM).	[36]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Lumican (LUM).	[37]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Lumican (LUM).	[38]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Lumican (LUM).	[39]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Lumican (LUM).	[40]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Lumican (LUM).	[41]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Lumican (LUM).	[42]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Lumican (LUM).	[43]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Lumican (LUM).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lumican (LUM).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Lumican (LUM).	[46]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Lumican (LUM).	[47]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Lumican (LUM).	[49]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Lumican (LUM).	[50]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Lumican (LUM).	[51]
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⏷ Show the Full List of 19 Drug(s)

References

1	Lumican is overexpressed in lung adenocarcinoma pleural effusions.PLoS One. 2015 May 11;10(5):e0126458. doi: 10.1371/journal.pone.0126458. eCollection 2015.
2	First experience in Switzerland in Phe508del homozygous cystic fibrosis patients with end-stage pulmonary disease enrolled in a lumacaftor-ivacaftor therapy trial - preliminary results.Swiss Med Wkly. 2018 Feb 16;148:w14593. doi: 10.4414/smw.2018.14593. eCollection 2018.
3	Hypoxia-induced autophagy of stellate cells inhibits expression and secretion of lumican into microenvironment of pancreatic ductal adenocarcinoma.Cell Death Differ. 2019 Jan;26(2):382-393. doi: 10.1038/s41418-018-0207-3. Epub 2018 Oct 3.
4	Association of SLRPs with carotid artery atherosclerosis in essential hypertensive patients.J Hum Hypertens. 2018 Sep;32(8-9):564-571. doi: 10.1038/s41371-018-0077-7. Epub 2018 Jun 5.
5	Small Leucine Rich Proteoglycans (decorin, biglycan and lumican) in cancer.Clin Chim Acta. 2019 Apr;491:1-7. doi: 10.1016/j.cca.2019.01.003. Epub 2019 Jan 7.
6	Lumican regulates osteosarcoma cell adhesion by modulating TGF2 activity.Int J Biochem Cell Biol. 2011 Jun;43(6):928-35. doi: 10.1016/j.biocel.2011.03.008. Epub 2011 Mar 21.
7	Epithelial-to-mesenchymal transition and invadopodia markers in breast cancer: Lumican a key regulator.Semin Cancer Biol. 2020 May;62:125-133. doi: 10.1016/j.semcancer.2019.08.003. Epub 2019 Aug 8.
8	Genetic variation in stromal proteins decorin and lumican with breast cancer: investigations in two case-control studies.Breast Cancer Res. 2008;10(6):R98. doi: 10.1186/bcr2201. Epub 2008 Nov 26.
9	Lumican and versican protein expression are associated with colorectal adenoma-to-carcinoma progression.PLoS One. 2017 May 8;12(5):e0174768. doi: 10.1371/journal.pone.0174768. eCollection 2017.
10	The extracellular matrix proteoglycan lumican improves survival and counteracts cardiac dilatation and failure in mice subjected to pressure overload.Sci Rep. 2019 Jun 24;9(1):9206. doi: 10.1038/s41598-019-45651-9.
11	Expression and roles of lumican in lung adenocarcinoma and squamous cell carcinoma.Int J Oncol. 2008 Dec;33(6):1177-85.
12	The significance of lumican expression in ovarian cancer drug-resistant cell lines.Oncotarget. 2017 Aug 10;8(43):74466-74478. doi: 10.18632/oncotarget.20169. eCollection 2017 Sep 26.
13	Facioscapulohumeral muscular dystrophy (FSHD) myoblasts demonstrate increased susceptibility to oxidative stress.Neuromuscul Disord. 2003 May;13(4):322-33. doi: 10.1016/s0960-8966(02)00284-5.
14	Lumican, an extracellular matrix proteoglycan, is a novel requisite for hepatic fibrosis.Lab Invest. 2012 Dec;92(12):1712-25. doi: 10.1038/labinvest.2012.121. Epub 2012 Sep 24.
15	Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV(1).J Cyst Fibros. 2019 Jan;18(1):94-101. doi: 10.1016/j.jcf.2018.07.011. Epub 2018 Aug 23.
16	Quantitative analysis of core fucosylation of serum proteins in liver diseases by LC-MS-MRM.J Proteomics. 2018 Oct 30;189:67-74. doi: 10.1016/j.jprot.2018.02.003. Epub 2018 Feb 7.
17	Downregulation of lumican accelerates lung cancer cell invasion through p120 catenin.Cell Death Dis. 2018 Apr 1;9(4):414. doi: 10.1038/s41419-017-0212-3.
18	Lumican is upregulated in osteoarthritis and contributes to TLR4-induced pro-inflammatory activation of cartilage degradation and macrophage polarization.Osteoarthritis Cartilage. 2020 Jan;28(1):92-101. doi: 10.1016/j.joca.2019.10.011. Epub 2019 Nov 9.
19	Association analysis of polymorphisms in lumican gene and systemic lupus erythematosus in a Taiwan Chinese Han population.J Rheumatol. 2011 Nov;38(11):2376-81. doi: 10.3899/jrheum.101310. Epub 2011 Sep 1.
20	Lumican expression in gastric cancer and its association with biological behavior and prognosis.Oncol Lett. 2017 Nov;14(5):5235-5240. doi: 10.3892/ol.2017.6842. Epub 2017 Aug 28.
21	Proteomic Analysis of the Myocardium in Hypertrophic Obstructive Cardiomyopathy.Circ Genom Precis Med. 2018 Dec;11(12):e001974. doi: 10.1161/CIRCGEN.117.001974.
22	Mitogen Inducible Gene-6 Is a Prognostic Marker for Patients with Colorectal Liver Metastases.Transl Oncol. 2019 Mar;12(3):550-560. doi: 10.1016/j.tranon.2018.12.007. Epub 2019 Jan 9.
23	Diet-dependent function of the extracellular matrix proteoglycan Lumican in obesity and glucose homeostasis.Mol Metab. 2019 Jan;19:97-106. doi: 10.1016/j.molmet.2018.10.007. Epub 2018 Oct 23.
24	Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide.Sci Rep. 2017 Aug 9;7(1):7700. doi: 10.1038/s41598-017-07043-9.
25	Overexpression of lumican affects the migration of human colon cancer cells through up-regulation of gelsolin and filamentous actin reorganization.Exp Cell Res. 2012 Nov 1;318(18):2312-23. doi: 10.1016/j.yexcr.2012.07.005. Epub 2012 Jul 16.
26	Myocardial Injury Is Distinguished from Stable Angina by a Set of Candidate Plasma Biomarkers Identified Using iTRAQ/MRM-Based Approach.J Proteome Res. 2018 Jan 5;17(1):499-515. doi: 10.1021/acs.jproteome.7b00651. Epub 2017 Nov 7.
27	Modeling long-term health outcomes of patients with cystic fibrosis homozygous for F508del-CFTR treated with lumacaftor/ivacaftor.Ther Adv Respir Dis. 2019 Jan-Dec;13:1753466618820186. doi: 10.1177/1753466618820186.
28	Lumican suppresses cell proliferation and aids Fas-Fas ligand mediated apoptosis: implications in the cornea.Exp Eye Res. 2004 May;78(5):957-71. doi: 10.1016/j.exer.2003.12.006.
29	Accessing key steps of human tumor progression in vivo by using an avian embryo model.Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1643-8. doi: 10.1073/pnas.0408622102. Epub 2005 Jan 21.
30	Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.Nat Commun. 2018 May 14;9(1):1864. doi: 10.1038/s41467-018-03646-6.
31	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.
32	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.
33	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
34	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
35	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.
36	Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
37	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
38	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
39	Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
40	Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
41	Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
42	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
43	Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
44	Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
45	Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
46	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.
47	Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
48	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.
49	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.
50	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.
51	3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.
52	Microarray-based detection and expression analysis of extracellular matrix proteins in drug?resistant ovarian cancer cell lines. Oncol Rep. 2014 Nov;32(5):1981-90. doi: 10.3892/or.2014.3468. Epub 2014 Sep 9.