Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0E4H2D)

• DOT Name: Protein SSX4 (SSX4)
• Synonyms: Cancer/testis antigen 5.4; CT5.4
• Gene Name: SSX4
• Related Disease:
  Advanced cancer
  Brain neoplasm
  Intrahepatic cholangiocarcinoma
  Lung cancer
  Neoplasm
  Plasma cell myeloma
  Melanoma
  Neuroblastoma
  Testicular cancer
  Synovial sarcoma
• UniProt ID: SSX4_HUMAN
• Pfam ID: PF09514
• Sequence:
  MNGDDAFARRPRDDAQISEKLRKAFDDIAKYFSKKEWEKMKSSEKIVYVYMKLNYEVMTK
  LGFKVTLPPFMRSKRAADFHGNDFGNDRNHRNQVERPQMTFGSLQRIFPKIMPKKPAEEE
  NGLKEVPEASGPQNDGKQLCPPGNPSTLEKINKTSGPKRGKHAWTHRLRERKQLVVYEEI
  SDPEEDDE
• Function: Could act as a modulator of transcription.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[2]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[5]
Melanoma	DIS1RRCY	moderate	Biomarker	[6]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[7]
Testicular cancer	DIS6HNYO	moderate	Altered Expression	[8]
Synovial sarcoma	DISEZJS7	Disputed	Genetic Variation	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein SSX4 (SSX4).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein SSX4 (SSX4).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein SSX4 (SSX4).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein SSX4 (SSX4).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein SSX4 (SSX4).	[14]

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 decreases the methylation of Protein SSX4 (SSX4).	[13]

References

• [1] SSX2-4 expression in early-stage non-small cell lung cancer.Tissue Antigens. 2014 May;83(5):344-9. doi: 10.1111/tan.12340. Epub 2014 Mar 20.
• [2] Identification and functional characterization of glioma-specific promoters and their application in suicide gene therapy.J Neurooncol. 2011 Sep;104(2):497-507. doi: 10.1007/s11060-010-0522-0. Epub 2011 Feb 24.
• [3] Expression of cancer-testis antigen (CTA) genes in intrahepatic cholangiocarcinoma.Ann Surg Oncol. 2004 Oct;11(10):934-40. doi: 10.1245/ASO.2004.01.029.
• [4] Expression of cancer-testis antigens in lung cancer: definition of bromodomain testis-specific gene (BRDT) as a new CT gene, CT9.Cancer Lett. 2000 Mar 31;150(2):155-64. doi: 10.1016/s0304-3835(99)00385-7.
• [5] SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs.J Immunother. 2005 Nov-Dec;28(6):564-75. doi: 10.1097/01.cji.0000175685.36239.e5.
• [6] Effects of CT-Xp gene knock down in melanoma cell lines.Oncotarget. 2013 Apr;4(4):531-41. doi: 10.18632/oncotarget.921.
• [7] Expression of SSX-2 and SSX-4 genes in neuroblastoma.Int J Biol Markers. 2002 Oct-Dec;17(4):219-23. doi: 10.1177/172460080201700401.
• [8] Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancer.Int J Cancer. 2006 Feb 1;118(3):696-703. doi: 10.1002/ijc.21352.
• [9] Clinical application of RNA sequencing in sarcoma diagnosis: An institutional experience.Medicine (Baltimore). 2019 Jun;98(25):e16031. doi: 10.1097/MD.0000000000016031.
• [10] 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.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Treatment of chronic lymphocytic leukemia with a hypomethylating agent induces expression of NXF2, an immunogenic cancer testis antigen. Clin Cancer Res. 2009 May 15;15(10):3406-15. doi: 10.1158/1078-0432.CCR-08-2099. Epub 2009 Apr 28.
• [13] 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.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.