Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAK3TMO)

• DOT Name: Protein SCAI (SCAI)
• Synonyms: Suppressor of cancer cell invasion protein
• Gene Name: SCAI
• Related Disease:
  Advanced cancer
  Bone osteosarcoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioma
  Lung cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Renal fibrosis
  Thyroid gland papillary carcinoma
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Coronary atherosclerosis
  Coronary heart disease
• UniProt ID: SCAI_HUMAN
• Pfam ID: PF12070
• Sequence:
  MVRGARQPQQPRSRLAPRLTGTVEKPPRKRRSRTEFALKEIMSSGGAEDDIPQGERKTVT
  DFCYLLDKSKQLFNGLRDLPQYGQKQWQSYFGRTFDVYTKLWKFQQQHRQVLDNRYGLKR
  WQIGEIASKIGQLYYHYYLRTSETSYLNEAFSFYSAIRQRSYYSQVNKEDRPELVVKKLR
  YYARFIVVCLLLNKMDVVKDLVKELSDEIEDYTHRFNTEDQVEWNLVLQEVAAFIEADPV
  MVLNDDNTIVITSNRLAETGAPLLEQGMIVGQLSLADALIIGNCNNQVKFSELTVDMFRM
  LQALEREPMNLASQMNKPGMQESADKPTRRENPHKYLLYKPTFSQLYTFLAASFKELPAN
  SVLLIYLSATGVFPTGRSDSEGPYDFGGVLTNSNRDIINGDAIHKRNQSHKEMHCLHPGD
  LYPFTRKPLFIIVDSSNSVAYKNFTNLFGQPLVCLLSPTAYPKALQDQSQRGSLFTLFLN
  NPLMAFLFVSGLSSMRRGLWEKCQEYLRKINRDIAQLLTHSRSIDQAFLQFFGDEFLRLL
  LTRFIFCSATMRMHKIFRETRNYPESYPQLPRDETVENPHLQKHILELASILDVRNVFFE
  NTIDDY
• Function: Tumor suppressor which functions to suppress MRTFA-induced SRF transcriptional activity. May function in the RHOA-DIAPH1 signal transduction pathway and regulate cell migration through transcriptional regulation of ITGB1.
• Reactome Pathway: RHO GTPases Activate Formins (R-HSA-5663220)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[2]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Renal fibrosis	DISMHI3I	Strong	Altered Expression	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[8]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[9]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[9]

5 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 SCAI (SCAI).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein SCAI (SCAI).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein SCAI (SCAI).	[12]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Protein SCAI (SCAI).	[13]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Protein SCAI (SCAI).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein SCAI (SCAI).	[14]

References

• [1] Alterations in SCAI Expression during Cell Plasticity, Fibrosis and Cancer.Pathol Oncol Res. 2018 Jul;24(3):641-651. doi: 10.1007/s12253-017-0293-4. Epub 2017 Aug 16.
• [2] Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI.Oncol Res. 2019 Sep 23;27(9):979-986. doi: 10.3727/096504018X15336368805108. Epub 2018 Aug 8.
• [3] Circular RNA Cdr1as Upregulates SCAI to Suppress Cisplatin Resistance in Ovarian Cancer via miR-1270 Suppression.Mol Ther Nucleic Acids. 2019 Dec 6;18:24-33. doi: 10.1016/j.omtn.2019.07.012. Epub 2019 Jul 29.
• [4] MicroRNA-1290 promotes esophageal squamous cell carcinoma cell proliferation and metastasis.World J Gastroenterol. 2015 Mar 21;21(11):3245-55. doi: 10.3748/wjg.v21.i11.3245.
• [5] Downregulation of SCAI enhances glioma cell invasion and stem cell like phenotype by activating Wnt/-catenin signaling.Biochem Biophys Res Commun. 2014 May 30;448(2):206-11. doi: 10.1016/j.bbrc.2014.04.098. Epub 2014 Apr 29.
• [6] MicroRNA-1270 modulates papillary thyroid cancer cell development by regulating SCAI.Biomed Pharmacother. 2019 Jan;109:2357-2364. doi: 10.1016/j.biopha.2018.08.150. Epub 2018 Nov 30.
• [7] Inhibition of RIF1 by SCAI Allows BRCA1-Mediated Repair.Cell Rep. 2017 Jul 11;20(2):297-307. doi: 10.1016/j.celrep.2017.06.056.
• [8] MiR-425-5p promotes invasion and metastasis of hepatocellular carcinoma cells through SCAI-mediated dysregulation of multiple signaling pathways.Oncotarget. 2017 May 9;8(19):31745-31757. doi: 10.18632/oncotarget.15958.
• [9] ScaI atrial natriuretic peptide gene polymorphisms and their possible association with postoperative atrial fibrillation - a preliminary report.Arch Med Sci. 2017 Apr 1;13(3):568-574. doi: 10.5114/aoms.2016.58270. Epub 2016 May 12.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] 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.
• [13] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [14] 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.
• [15] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.