Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5DTDO2)

DOT Name Protein MTSS 1 (MTSS1)
Synonyms Metastasis suppressor YGL-1; Metastasis suppressor protein 1; Missing in metastasis protein
Gene Name MTSS1
Related Disease
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Adult lymphoma ( )
Arteriosclerosis ( )
Atherosclerosis ( )
B-cell lymphoma ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac arrest ( )
Cerebellar ataxia ( )
Colorectal carcinoma ( )
Esophageal cancer ( )
Esophageal squamous cell carcinoma ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Juvenile idiopathic arthritis ( )
Lung adenocarcinoma ( )
Lymphoma ( )
Matthew-Wood syndrome ( )
Medulloblastoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Pediatric lymphoma ( )
Stomach cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Breast neoplasm ( )
Gastric cancer ( )
Melanoma ( )
Plasma cell myeloma ( )
Adult glioblastoma ( )
Epithelial ovarian cancer ( )
Gastric neoplasm ( )
Glioblastoma multiforme ( )
Hereditary diffuse gastric adenocarcinoma ( )
Non-hodgkin lymphoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic cancer ( )
Pancreatic ductal carcinoma ( )
Small lymphocytic lymphoma ( )
UniProt ID
MTSS1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2D1K
Pfam ID
PF08397 ; PF02205
Sequence
MEAVIEKECSALGGLFQTIISDMKGSYPVWEDFINKAGKLQSQLRTTVVAAAAFLDAFQK
VADMATNTRGGTREIGSALTRMCMRHRSIEAKLRQFSSALIDCLINPLQEQMEEWKKVAN
QLDKDHAKEYKKARQEIKKKSSDTLKLQKKAKKGRGDIQPQLDSALQDVNDKYLLLEETE
KQAVRKALIEERGRFCTFISMLRPVIEEEISMLGEITHLQTISEDLKSLTMDPHKLPSSS
EQVILDLKGSDYSWSYQTPPSSPSTTMSRKSSVCSSLNSVNSSDSRSSGSHSHSPSSHYR
YRSSNLAQQAPVRLSSVSSHDSGFISQDAFQSKSPSPMPPEAPNQLSNGFSHYSLSSESH
VGPTGAGLFPHCLPASRLLPRVTSVHLPDYAHYYTIGPGMFPSSQIPSWKDWAKPGPYDQ
PLVNTLQRRKEKREPDPNGGGPTTASGPPAAAEEAQRPRSMTVSAATRPGEEMEACEELA
LALSRGLQLDTQRSSRDSLQCSSGYSTQTTTPCCSEDTIPSQVSDYDYFSVSGDQEADQQ
EFDKSSTIPRNSDISQSYRRMFQAKRPASTAGLPTTLGPAMVTPGVATIRRTPSTKPSVR
RGTIGAGPIPIKTPVIPVKTPTVPDLPGVLPAPPDGPEERGEHSPESPSVGEGPQGVTSM
PSSMWSGQASVNPPLPGPKPSIPEEHRQAIPESEAEDQEREPPSATVSPGQIPESDPADL
SPRDTPQGEDMLNAIRRGVKLKKTTTNDRSAPRFS
Function May be related to cancer progression or tumor metastasis in a variety of organ sites, most likely through an interaction with the actin cytoskeleton.
Tissue Specificity Expressed in many tissues, including spleen, thymus, prostate, testis, uterus, colon, and peripheral blood.

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute monocytic leukemia DIS28NEL Strong Biomarker [1]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [1]
Adult lymphoma DISK8IZR Strong Biomarker [2]
Arteriosclerosis DISK5QGC Strong Genetic Variation [3]
Atherosclerosis DISMN9J3 Strong Genetic Variation [3]
B-cell lymphoma DISIH1YQ Strong Biomarker [4]
Bladder cancer DISUHNM0 Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Biomarker [6]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Cardiac arrest DIS9DIA4 Strong Biomarker [7]
Cerebellar ataxia DIS9IRAV Strong Genetic Variation [7]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [8]
Esophageal cancer DISGB2VN Strong Altered Expression [9]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [9]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [10]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [11]
Juvenile idiopathic arthritis DISQZGBV Strong Biomarker [12]
Lung adenocarcinoma DISD51WR Strong Altered Expression [13]
Lymphoma DISN6V4S Strong Altered Expression [2]
Matthew-Wood syndrome DISA7HR7 Strong Altered Expression [14]
Medulloblastoma DISZD2ZL Strong Altered Expression [15]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [16]
Neoplasm DISZKGEW Strong Biomarker [17]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [18]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [19]
Pediatric lymphoma DIS51BK2 Strong Biomarker [2]
Stomach cancer DISKIJSX Strong Altered Expression [20]
Urinary bladder cancer DISDV4T7 Strong Biomarker [5]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [5]
Breast neoplasm DISNGJLM moderate Altered Expression [21]
Gastric cancer DISXGOUK moderate Altered Expression [20]
Melanoma DIS1RRCY moderate Biomarker [22]
Plasma cell myeloma DIS0DFZ0 moderate Altered Expression [23]
Adult glioblastoma DISVP4LU Limited Posttranslational Modification [24]
Epithelial ovarian cancer DIS56MH2 Limited Altered Expression [25]
Gastric neoplasm DISOKN4Y Limited Biomarker [26]
Glioblastoma multiforme DISK8246 Limited Genetic Variation [24]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Limited Biomarker [26]
Non-hodgkin lymphoma DISS2Y8A Limited Biomarker [2]
Ovarian cancer DISZJHAP Limited Altered Expression [25]
Ovarian neoplasm DISEAFTY Limited Altered Expression [25]
Pancreatic cancer DISJC981 Limited Biomarker [27]
Pancreatic ductal carcinoma DIS26F9Q Limited Biomarker [14]
Small lymphocytic lymphoma DIS30POX Limited Altered Expression [28]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Protein MTSS 1 (MTSS1). [29]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Protein MTSS 1 (MTSS1). [44]
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17 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 Protein MTSS 1 (MTSS1). [30]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Protein MTSS 1 (MTSS1). [31]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protein MTSS 1 (MTSS1). [32]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Protein MTSS 1 (MTSS1). [33]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Protein MTSS 1 (MTSS1). [34]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Protein MTSS 1 (MTSS1). [35]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Protein MTSS 1 (MTSS1). [36]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Protein MTSS 1 (MTSS1). [37]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Protein MTSS 1 (MTSS1). [38]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Protein MTSS 1 (MTSS1). [26]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Protein MTSS 1 (MTSS1). [40]
Rigosertib DMOSTXF Phase 3 Rigosertib increases the expression of Protein MTSS 1 (MTSS1). [41]
Tanespimycin DMNLQHK Phase 2 Tanespimycin increases the expression of Protein MTSS 1 (MTSS1). [42]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Protein MTSS 1 (MTSS1). [43]
Scriptaid DM9JZ21 Preclinical Scriptaid affects the expression of Protein MTSS 1 (MTSS1). [45]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Protein MTSS 1 (MTSS1). [46]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Protein MTSS 1 (MTSS1). [47]
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⏷ Show the Full List of 17 Drug(s)

References

1 Identification of the Adapter Molecule MTSS1 as a Potential Oncogene-Specific Tumor Suppressor in Acute Myeloid Leukemia.PLoS One. 2015 May 21;10(5):e0125783. doi: 10.1371/journal.pone.0125783. eCollection 2015.
2 Mice deficient in MIM expression are predisposed to lymphomagenesis.Oncogene. 2012 Jul 26;31(30):3561-8. doi: 10.1038/onc.2011.509. Epub 2011 Nov 14.
3 Identification of a new locus and validation of previously reported loci showing differential methylation associated with smoking. The REGICOR study.Epigenetics. 2015;10(12):1156-65. doi: 10.1080/15592294.2015.1115175.
4 Expression and clinical significance of miR-23a and MTSS1 in diffuse large B-cell lymphoma.Oncol Lett. 2018 Jul;16(1):371-377. doi: 10.3892/ol.2018.8657. Epub 2018 May 7.
5 Reduced Expression of Metastasis Suppressor-1 (MTSS1) Accelerates Progression of Human Bladder Uroepithelium Cell Carcinoma.Anticancer Res. 2017 Aug;37(8):4499-4505. doi: 10.21873/anticanres.11846.
6 MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer.Cell Death Dis. 2018 Mar 1;9(3):344. doi: 10.1038/s41419-018-0364-9.
7 MTSS1/Src family kinase dysregulation underlies multiple inherited ataxias.Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12407-E12416. doi: 10.1073/pnas.1816177115. Epub 2018 Dec 7.
8 Role of Akt2 in regulation of metastasis suppressor 1 expression and colorectal cancer metastasis.Oncogene. 2017 Jun 1;36(22):3104-3118. doi: 10.1038/onc.2016.460. Epub 2017 Jan 9.
9 The impact of Metastasis Suppressor-1, MTSS1, on oesophageal squamous cell carcinoma and its clinical significance.J Transl Med. 2011 Jun 22;9:95. doi: 10.1186/1479-5876-9-95.
10 Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma.J Exp Clin Cancer Res. 2016 May 26;35(1):85. doi: 10.1186/s13046-016-0361-8.
11 Missing-in-metastasis B (MIM-B) combined with caveolin-1 promotes metastasis of hepatocellular carcinoma.Oncotarget. 2017 Sep 8;8(56):95450-95465. doi: 10.18632/oncotarget.20735. eCollection 2017 Nov 10.
12 Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
13 Metastasis suppressor 1 (MTSS1) expression is associated with reduced in-vivo metastasis and enhanced patient survival in lung adenocarcinoma.Clin Exp Metastasis. 2018 Feb;35(1-2):15-23. doi: 10.1007/s10585-017-9869-3. Epub 2017 Dec 7.
14 PTEN-Dependent Stabilization of MTSS1 Inhibits Metastatic Phenotype in Pancreatic Ductal Adenocarcinoma.Neoplasia. 2018 Jan;20(1):12-24. doi: 10.1016/j.neo.2017.10.004. Epub 2017 Nov 23.
15 Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor 1 (Mtss1) in normal and transformed cerebellar cells.BMC Dev Biol. 2007 Oct 9;7:111. doi: 10.1186/1471-213X-7-111.
16 Downregulation of metastasis suppressor 1(MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer.BMC Cancer. 2010 Aug 15;10:428. doi: 10.1186/1471-2407-10-428.
17 MTSS1 hypermethylation is associated with prostate cancer progression.J Cell Physiol. 2020 Mar;235(3):2687-2697. doi: 10.1002/jcp.29172. Epub 2019 Sep 20.
18 Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes.BMC Genet. 2017 Dec 8;18(1):105. doi: 10.1186/s12863-017-0572-9.
19 Study on molecular mechanism of MiRNA-29a in promoting proliferation and invasion of non-small-cell lung cancer by inhibiting MTSS1.Eur Rev Med Pharmacol Sci. 2018 Sep;22(17):5531-5538. doi: 10.26355/eurrev_201809_15814.
20 Metastasis suppressor protein 1 regulated by PTEN suppresses invasion, migration, and EMT of gastric carcinoma by inactivating PI3K/AKT signaling.J Cell Biochem. 2019 Mar;120(3):3447-3454. doi: 10.1002/jcb.27618. Epub 2018 Sep 23.
21 p63 controls cell migration and invasion by transcriptional regulation of MTSS1.Oncogene. 2016 Mar 24;35(12):1602-8. doi: 10.1038/onc.2015.230. Epub 2015 Jun 29.
22 MTSS1 is a metastasis driver in a subset of human melanomas.Nat Commun. 2014 Mar 17;5:3465. doi: 10.1038/ncomms4465.
23 MicroRNA-324-5p suppresses the migration and invasion of MM cells by inhibiting the SCF(-TrCP) E3 ligase.Oncol Lett. 2018 Oct;16(4):5331-5338. doi: 10.3892/ol.2018.9245. Epub 2018 Aug 1.
24 MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility.Transl Oncol. 2017 Feb;10(1):70-79. doi: 10.1016/j.tranon.2016.11.006. Epub 2016 Dec 15.
25 Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma.Mod Pathol. 2012 Dec;25(12):1644-53. doi: 10.1038/modpathol.2012.118. Epub 2012 Jul 13.
26 Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
27 Loss of MTSS1 results in increased metastatic potential in pancreatic cancer.Oncotarget. 2017 Mar 7;8(10):16473-16487. doi: 10.18632/oncotarget.14869.
28 Computational analysis of the evolutionarily conserved Missing In Metastasis/Metastasis Suppressor 1 gene predicts novel interactions, regulatory regions and transcriptional control.Sci Rep. 2019 Mar 11;9(1):4155. doi: 10.1038/s41598-019-40697-1.
29 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.
30 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.
31 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.
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 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.
35 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.
36 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.
37 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
38 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
39 Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
40 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
41 ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
42 Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype-associated gene expression signatures. Cancer. 2009 Aug 15;115(16):3738-48. doi: 10.1002/cncr.24417.
43 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
44 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.
45 Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
46 Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
47 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.