Details of Drug Off-Target (DOT)

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

• DOT Name: Fascin (FSCN1)
• Synonyms: 55 kDa actin-bundling protein; Singed-like protein; p55
• Gene Name: FSCN1
• UniProt ID: FSCN1_HUMAN
• PDB ID: 1DFC; 3LLP; 3P53; 4GOV; 4GOY; 4GP0; 4GP3; 6B0T; 6I0Z; 6I10; 6I11; 6I12; 6I13; 6I14; 6I15; 6I16; 6I17; 6I18; 7ZAU
• Pfam ID: PF06268
• Sequence:
  MTANGTAEAVQIQFGLINCGNKYLTAEAFGFKVNASASSLKKKQIWTLEQPPDEAGSAAV
  CLRSHLGRYLAADKDGNVTCEREVPGPDCRFLIVAHDDGRWSLQSEAHRRYFGGTEDRLS
  CFAQTVSPAEKWSVHIAMHPQVNIYSVTRKRYAHLSARPADEIAVDRDVPWGVDSLITLA
  FQDQRYSVQTADHRFLRHDGRLVARPEPATGYTLEFRSGKVAFRDCEGRYLAPSGPSGTL
  KAGKATKVGKDELFALEQSCAQVVLQAANERNVSTRQGMDLSANQDEETDQETFQLEIDR
  DTKKCAFRTHTGKYWTLTATGGVQSTASSKNASCYFDIEWRDRRITLRASNGKFVTSKKN
  GQLAASVETAGDSELFLMKLINRPIIVFRGEHGFIGCRKVTGTLDANRSSYDVFQLEFND
  GAYNIKDSTGKYWTVGSDSAVTSSGDTPVDFFFEFCDYNKVAIKVGGRYLKGDHAGVLKA
  SAETVDPASLWEY
• Function: Actin-binding protein that contains 2 major actin binding sites. Organizes filamentous actin into parallel bundles. Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers. Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration. Mediates reorganization of the actin cytoskeleton and axon growth cone collapse in response to NGF.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: MicroR.s in cancer (hsa05206)
• Reactome Pathway: Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Fascin (FSCN1) increases the response to substance of Paclitaxel.	[25]

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 Fascin (FSCN1).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Fascin (FSCN1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fascin (FSCN1).	[19]

20 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 Fascin (FSCN1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fascin (FSCN1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Fascin (FSCN1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fascin (FSCN1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Fascin (FSCN1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Fascin (FSCN1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Fascin (FSCN1).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Fascin (FSCN1).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fascin (FSCN1).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Fascin (FSCN1).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Fascin (FSCN1).	[13]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Fascin (FSCN1).	[14]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Fascin (FSCN1).	[15]
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate increases the expression of Fascin (FSCN1).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Fascin (FSCN1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fascin (FSCN1).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Fascin (FSCN1).	[21]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Fascin (FSCN1).	[22]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Fascin (FSCN1).	[23]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Fascin (FSCN1).	[24]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Fascin (FSCN1).	[18]

References

• [1] 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.
• [2] 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.
• [3] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [7] 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.
• [8] Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4578-83.
• [9] Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
• [10] Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells. Biochemistry. 2007 Aug 7;46(31):8920-32. doi: 10.1021/bi7000328. Epub 2007 Jul 14.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [14] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [15] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [16] 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.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [19] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [20] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [21] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [22] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [23] 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.
• [24] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [25] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.