Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR8Y32X)

• DOT Name: Lipolysis-stimulated lipoprotein receptor (LSR)
• Synonyms: Angulin-1
• Gene Name: LSR
• Related Disease:
  Carcinoma
  Undifferentiated carcinoma
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal neoplasm
  Dysbetalipoproteinemia
  Endometrium adenocarcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Neoplasm
  Non-insulin dependent diabetes
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Advanced cancer
  Endometrial cancer
  Endometrial carcinoma
  Gastric cancer
  Stomach cancer
  Stroke
• UniProt ID: LSR_HUMAN
• Pfam ID: PF05624
• Sequence:
  MQQDGLGVGTRNGSGKGRSVHPSWPWCAPRPLRYFGRDARARRAQTAAMALLAGGLSRGL
  GSHPAAAGRDAVVFVWLLLSTWCTAPARAIQVTVSNPYHVVILFQPVTLPCTYQMTSTPT
  QPIVIWKYKSFCRDRIADAFSPASVDNQLNAQLAAGNPGYNPYVECQDSVRTVRVVATKQ
  GNAVTLGDYYQGRRITITGNADLTFDQTAWGDSGVYYCSVVSAQDLQGNNEAYAELIVLG
  RTSGVAELLPGFQAGPIEDWLFVVVVCLAAFLIFLLLGICWCQCCPHTCCCYVRCPCCPD
  KCCCPEALYAAGKAATSGVPSIYAPSTYAHLSPAKTPPPPAMIPMGPAYNGYPGGYPGDV
  DRSSSAGGQGSYVPLLRDTDSSVASEVRSGYRIQASQQDDSMRVLYYMEKELANFDPSRP
  GPPSGRVERAMSEVTSLHEDDWRSRPSRGPALTPIRDEEWGGHSPRSPRGWDQEPAREQA
  GGGWRARRPRARSVDALDDLTPPSTAESGSRSPTSNGGRSRAYMPPRSRSRDDLYDQDDS
  RDFPRSRDPHYDDFRSRERPPADPRSHHHRTRDPRDNGSRSGDLPYDGRLLEEAVRKKGS
  EERRRPHKEEEEEAYYPPAPPPYSETDSQASRERRLKKNLALSRESLVV
• Function: Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells. Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions.
• Reactome Pathway:
  VLDL clearance (R-HSA-8964046)
  LDL clearance (R-HSA-8964038)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Undifferentiated carcinoma	DISIAZST	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Altered Expression	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[5]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[5]
Dysbetalipoproteinemia	DISNRSNM	Strong	Altered Expression	[4]
Endometrium adenocarcinoma	DISY6744	Strong	Altered Expression	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[10]
Obesity	DIS47Y1K	Strong	Biomarker	[10]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[11]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[12]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[12]
Gastric cancer	DISXGOUK	Limited	Biomarker	[13]
Stomach cancer	DISKIJSX	Limited	Biomarker	[13]
Stroke	DISX6UHX	Limited	Genetic Variation	[14]

3 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 Lipolysis-stimulated lipoprotein receptor (LSR).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Lipolysis-stimulated lipoprotein receptor (LSR).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lipolysis-stimulated lipoprotein receptor (LSR).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[17]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[19]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[20]
Selenium	DM25CGV	Approved	Selenium increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[21]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[22]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Lipolysis-stimulated lipoprotein receptor (LSR).	[27]

References

• [1] Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
• [2] Discriminating Alzheimer's disease progression using a new hippocampal marker from T1-weighted MRI: The local surface roughness.Hum Brain Mapp. 2019 Apr 1;40(5):1666-1676. doi: 10.1002/hbm.24478. Epub 2018 Nov 19.
• [3] Nuclear Localized LSR: A Novel Regulator of Breast Cancer Behavior and Tumorigenesis.Mol Cancer Res. 2017 Feb;15(2):165-178. doi: 10.1158/1541-7786.MCR-16-0085-T. Epub 2016 Nov 17.
• [4] Effect of LSR polymorphism on blood lipid levels and age-specific epistatic interaction with the APOE common polymorphism.Clin Genet. 2018 Apr;93(4):846-852. doi: 10.1111/cge.13181.
• [5] Prognostic value of LISCH7 mRNA in plasma and tumor of colon cancer patients.Clin Cancer Res. 2007 Nov 1;13(21):6351-8. doi: 10.1158/1078-0432.CCR-07-0882.
• [6] Loss of LSR affects epithelial barrier integrity and tumor xenograft growth of CaCo-2 cells.Oncotarget. 2017 Jun 6;8(23):37009-37022. doi: 10.18632/oncotarget.10425.
• [7] Downregulation of lipolysis-stimulated lipoprotein receptor promotes cell invasion via claudin-1-mediated matrix metalloproteinases in human endometrial cancer.Oncol Lett. 2017 Dec;14(6):6776-6782. doi: 10.3892/ol.2017.7038. Epub 2017 Sep 22.
• [8] A multiple mixed TiO(2) mesocrystal junction based PEC-colorimetric immunoassay for specific recognition of lipolysis stimulated lipoprotein receptor.Biosens Bioelectron. 2020 Jan 15;148:111809. doi: 10.1016/j.bios.2019.111809. Epub 2019 Oct 26.
• [9] Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.BMC Cancer. 2017 Aug 14;17(1):544. doi: 10.1186/s12885-017-3523-y.
• [10] The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.Oncotarget. 2016 May 10;7(19):27735-52. doi: 10.18632/oncotarget.8408.
• [11] Tricellular tight junction protein LSR/angulin-1 contributes to the epithelial barrier and malignancy in human pancreatic cancer cell line.Histochem Cell Biol. 2020 Jan;153(1):5-16. doi: 10.1007/s00418-019-01821-4. Epub 2019 Oct 24.
• [12] Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer.Sci Rep. 2017 Jan 10;7:37049. doi: 10.1038/srep37049.
• [13] Lipolysis-stimulated lipoprotein receptor overexpression is a novel predictor of poor clinical prognosis and a potential therapeutic target in gastric cancer.Oncotarget. 2018 Aug 31;9(68):32917-32928. doi: 10.18632/oncotarget.25952. eCollection 2018 Aug 31.
• [14] Wave intensity analysis in mice: age-related changes in WIA peaks and correlation with cardiac indexes.Heart Vessels. 2017 Apr;32(4):474-483. doi: 10.1007/s00380-016-0914-y. Epub 2016 Nov 3.
• [15] 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.
• [16] Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity. Endocrinology. 2008 Oct;149(10):4809-20. doi: 10.1210/en.2008-0035. Epub 2008 Jun 12.
• [17] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [18] 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.
• [19] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [20] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [21] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [24] 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.
• [25] 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.
• [26] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [27] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.