Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI57KDN)

• DOT Name: Protein S100-A11 (S100A11)
• Synonyms: Calgizzarin; Metastatic lymph node gene 70 protein; MLN 70; Protein S100-C; S100 calcium-binding protein A11
• Gene Name: S100A11
• Related Disease:
  Adenocarcinoma
  Adult glioblastoma
  Bipolar disorder
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Schizophrenia
  Squamous cell carcinoma
  Stomach cancer
  Thyroid gland papillary carcinoma
  Urinary bladder neoplasm
  Atopic dermatitis
  Intrahepatic cholangiocarcinoma
  Rheumatoid arthritis
  Bone osteosarcoma
  Osteosarcoma
  Adenoma
  Advanced cancer
  Chromosomal disorder
  Matthew-Wood syndrome
  Pancreatic cancer
• UniProt ID: S10AB_HUMAN
• PDB ID: 1V4Z; 1V50; 2LUC
• Pfam ID: PF00036 ; PF01023
• Sequence:
  MAKISSPTETERCIESLIAVFQKYAGKDGYNYTLSKTEFLSFMNTELAAFTKNQKDPGVL
  DRMMKKLDTNSDGQLDFSEFLNLIGGLAMACHDSFLKAVPSQKRT
• Function: Facilitates the differentiation and the cornification of keratinocytes.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Bipolar disorder	DISAM7J2	Strong	Altered Expression	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[11]
Gastric cancer	DISXGOUK	Strong	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
leukaemia	DISS7D1V	Strong	Altered Expression	[13]
Leukemia	DISNAKFL	Strong	Altered Expression	[13]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[14]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[14]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[16]
Osteoarthritis	DIS05URM	Strong	Biomarker	[17]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[10]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[10]
Prostate cancer	DISF190Y	Strong	Altered Expression	[18]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[18]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[19]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[3]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[14]
Stomach cancer	DISKIJSX	Strong	Biomarker	[5]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[20]
Atopic dermatitis	DISTCP41	moderate	Altered Expression	[21]
Intrahepatic cholangiocarcinoma	DIS6GOC8	moderate	Biomarker	[22]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[17]
Bone osteosarcoma	DIST1004	Disputed	Altered Expression	[23]
Osteosarcoma	DISLQ7E2	Disputed	Altered Expression	[23]
Adenoma	DIS78ZEV	Limited	Altered Expression	[8]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[24]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[25]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[26]
Pancreatic cancer	DISJC981	Limited	Biomarker	[27]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Protein S100-A11 (S100A11) increases the response to substance of Cisplatin.	[16]
Fluorouracil	DMUM7HZ	Approved	Protein S100-A11 (S100A11) increases the response to substance of Fluorouracil.	[16]
Mitomycin	DMH0ZJE	Approved	Protein S100-A11 (S100A11) affects the response to substance of Mitomycin.	[53]

26 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 Protein S100-A11 (S100A11).	[28]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein S100-A11 (S100A11).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein S100-A11 (S100A11).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein S100-A11 (S100A11).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein S100-A11 (S100A11).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein S100-A11 (S100A11).	[33]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein S100-A11 (S100A11).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein S100-A11 (S100A11).	[34]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein S100-A11 (S100A11).	[36]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein S100-A11 (S100A11).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein S100-A11 (S100A11).	[38]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein S100-A11 (S100A11).	[39]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein S100-A11 (S100A11).	[40]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protein S100-A11 (S100A11).	[41]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein S100-A11 (S100A11).	[43]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein S100-A11 (S100A11).	[44]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protein S100-A11 (S100A11).	[39]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Protein S100-A11 (S100A11).	[45]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Protein S100-A11 (S100A11).	[46]
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate increases the expression of Protein S100-A11 (S100A11).	[47]
Miglitol	DMXBQAM	Approved	Miglitol decreases the expression of Protein S100-A11 (S100A11).	[48]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein S100-A11 (S100A11).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein S100-A11 (S100A11).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein S100-A11 (S100A11).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein S100-A11 (S100A11).	[50]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein S100-A11 (S100A11).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein S100-A11 (S100A11).	[35]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Protein S100-A11 (S100A11).	[42]

References

• [1] Up-Regulation of S100A11 in Lung Adenocarcinoma - Its Potential Relationship with Cancer Progression.PLoS One. 2015 Nov 6;10(11):e0142642. doi: 10.1371/journal.pone.0142642. eCollection 2015.
• [2] S100A11 functions as novel oncogene in glioblastoma via S100A11/ANXA2/NF-B positive feedback loop.J Cell Mol Med. 2019 Oct;23(10):6907-6918. doi: 10.1111/jcmm.14574. Epub 2019 Aug 20.
• [3] Innate immune response is differentially dysregulated between bipolar disease and schizophrenia.Schizophr Res. 2015 Feb;161(2-3):215-21. doi: 10.1016/j.schres.2014.10.055. Epub 2014 Dec 6.
• [4] Evaluation and screening of mRNA S100A genes as serological biomarkers in different stages of bladder cancer in Egypt.Tumour Biol. 2016 Apr;37(4):4621-31. doi: 10.1007/s13277-015-4264-7. Epub 2015 Oct 27.
• [5] HGF-mediated S100A11 overexpression enhances proliferation and invasion of gastric cancer.Am J Transl Res. 2018 Nov 15;10(11):3385-3394. eCollection 2018.
• [6] S100 Calcium Binding Protein A11 (S100A11) Promotes The Proliferation, Migration And Invasion Of Cervical Cancer Cells, And Activates Wnt/-Catenin Signaling.Onco Targets Ther. 2019 Oct 22;12:8675-8685. doi: 10.2147/OTT.S225248. eCollection 2019.
• [7] LINC00997, a novel long noncoding RNA, contributes to metastasis via regulation of S100A11 in kidney renal clear cell carcinoma.Int J Biochem Cell Biol. 2019 Nov;116:105590. doi: 10.1016/j.biocel.2019.105590. Epub 2019 Aug 20.
• [8] Different expression of calgizzarin (S100A11) in normal colonic epithelium, adenoma and colorectal carcinoma.Int J Oncol. 2006 Jan;28(1):195-200.
• [9] Colorectal cancer progression correlates with upregulation of S100A11 expression in tumor tissues.Int J Colorectal Dis. 2008 Jul;23(7):675-82. doi: 10.1007/s00384-008-0464-6. Epub 2008 Mar 14.
• [10] Expression of S100A11 is a Prognostic Factor for Disease-free Survival and Overall Survival in Patients With High-grade Serous Ovarian Cancer.Appl Immunohistochem Mol Morphol. 2017 Feb;25(2):110-116. doi: 10.1097/PAI.0000000000000275.
• [11] Differential expression of S100 gene family in human esophageal squamous cell carcinoma.J Cancer Res Clin Oncol. 2004 Aug;130(8):480-6. doi: 10.1007/s00432-004-0555-x. Epub 2004 Jun 4.
• [12] EIF3C-enhanced exosome secretion promotes angiogenesis and tumorigenesis of human hepatocellular carcinoma.Oncotarget. 2018 Jan 11;9(17):13193-13205. doi: 10.18632/oncotarget.24149. eCollection 2018 Mar 2.
• [13] Expression profiles of signal transduction genes in ex vivo drug-resistant pediatric acute lymphoblastic leukemia.Anticancer Res. 2012 Feb;32(2):503-6.
• [14] Selective expression of S100A11 in lung cancer and its role in regulating proliferation of adenocarcinomas cells.Mol Cell Biochem. 2012 Jan;359(1-2):323-32. doi: 10.1007/s11010-011-1026-8. Epub 2011 Aug 23.
• [15] Determination of metastasis-associated proteins in non-small cell lung cancer by comparative proteomic analysis.Cancer Sci. 2007 Aug;98(8):1265-74. doi: 10.1111/j.1349-7006.2007.00514.x. Epub 2007 May 30.
• [16] Tudor staphylococcal nuclease drives chemoresistance of non-small cell lung carcinoma cells by regulating S100A11. Oncotarget. 2015 May 20;6(14):12156-73. doi: 10.18632/oncotarget.3495.
• [17] Calgizzarin (S100A11): a novel inflammatory mediator associated with disease activity of rheumatoid arthritis.Arthritis Res Ther. 2017 Apr 26;19(1):79. doi: 10.1186/s13075-017-1288-y.
• [18] Dysregulated expression of S100A11 (calgizzarin) in prostate cancer and precursor lesions.Hum Pathol. 2004 Nov;35(11):1385-91. doi: 10.1016/j.humpath.2004.07.015.
• [19] S100A11 regulates renal carcinoma cell proliferation, invasion, and migration via the EGFR/Akt signaling pathway and E-cadherin.Tumour Biol. 2017 May;39(5):1010428317705337. doi: 10.1177/1010428317705337.
• [20] Down-regulation of S100C is associated with bladder cancer progression and poor survival.Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):606-11.
• [21] Inhibition of S100A11 gene expression impairs keratinocyte response against vaccinia virus through downregulation of the IL-10 receptor 2 chain.J Allergy Clin Immunol. 2009 Aug;124(2):270-7, 277.e1. doi: 10.1016/j.jaci.2009.05.002. Epub 2009 Jul 3.
• [22] S100A11 promotes cell proliferation via P38/MAPK signaling pathway in intrahepatic cholangiocarcinoma.Mol Carcinog. 2019 Jan;58(1):19-30. doi: 10.1002/mc.22903. Epub 2018 Oct 21.
• [23] MicroRNA?2 inhibits the proliferation and migration, and increases the cisplatin sensitivity, of osteosarcoma cells.Mol Med Rep. 2018 May;17(5):7209-7217. doi: 10.3892/mmr.2018.8790. Epub 2018 Mar 20.
• [24] Proteomic analysis of the effects of cell culture density on the metastasis of breast cancer cells.Cell Biochem Funct. 2019 Mar;37(2):72-83. doi: 10.1002/cbf.3377. Epub 2019 Feb 18.
• [25] Analysis of S100A11 in DNA Damage Repair.Methods Mol Biol. 2019;1929:447-460. doi: 10.1007/978-1-4939-9030-6_28.
• [26] Upregulation of Mobility in Pancreatic Cancer Cells by Secreted S100A11 Through Activation of Surrounding Fibroblasts.Oncol Res. 2019 Aug 8;27(8):945-956. doi: 10.3727/096504019X15555408784978. Epub 2019 Apr 17.
• [27] Correlation between S100A11 and the TGF-(1)/SMAD4 pathway and its effects on the proliferation and apoptosis of pancreatic cancer cell line PANC-1.Mol Cell Biochem. 2019 Jan;450(1-2):53-64. doi: 10.1007/s11010-018-3372-2. Epub 2018 Jun 19.
• [28] 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.
• [29] 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.
• [30] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [31] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [32] 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.
• [33] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [34] 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.
• [35] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [36] 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.
• [37] 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.
• [38] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [39] 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.
• [40] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [41] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [42] Epigenetic deregulation of multiple S100 gene family members by differential hypomethylation and hypermethylation events in medulloblastoma. Br J Cancer. 2007 Jul 16;97(2):267-74. doi: 10.1038/sj.bjc.6603852. Epub 2007 Jun 19.
• [43] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [44] 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.
• [45] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [46] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [47] Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts. Cancer Lett. 2018 Aug 28;430:1-10. doi: 10.1016/j.canlet.2018.04.043. Epub 2018 May 5.
• [48] The -glucosidase inhibitor miglitol decreases glucose fluctuations and inflammatory cytokine gene expression in peripheral leukocytes of Japanese patients with type 2 diabetes mellitus. Metabolism. 2010 Dec;59(12):1816-22. doi: 10.1016/j.metabol.2010.06.006. Epub 2010 Jul 29.
• [49] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [50] 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.
• [51] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [52] Tudor staphylococcal nuclease drives chemoresistance of non-small cell lung carcinoma cells by regulating S100A11. Oncotarget. 2015 May 20;6(14):12156-73. doi: 10.18632/oncotarget.3495.
• [53] 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.