Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2Z6RLL)

DOT Name Protein SSX2 (SSX2)
Synonyms Cancer/testis antigen 5.2; CT5.2; Synovial sarcoma, X breakpoint 2; Tumor antigen HOM-MEL-40
Gene Name SSX2
Related Disease
Carcinoma of esophagus ( )
Esophageal cancer ( )
Neoplasm of esophagus ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Adult lymphoma ( )
Benign neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Chromosomal disorder ( )
Classic Hodgkin lymphoma ( )
Colon cancer ( )
Colorectal carcinoma ( )
Desmoplastic small round cell tumor ( )
Hepatocellular carcinoma ( )
Leiomyosarcoma ( )
Leukemia ( )
Lymphoma ( )
Malignant peripheral nerve sheath tumor ( )
Malignant soft tissue neoplasm ( )
Melanoma ( )
Melorheostosis ( )
Metastatic malignant neoplasm ( )
Metastatic prostate carcinoma ( )
Pediatric lymphoma ( )
Prostate carcinoma ( )
Sarcoma ( )
Seminoma ( )
Soft tissue neoplasm ( )
Soft tissue sarcoma ( )
Testicular cancer ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Bone osteosarcoma ( )
Neuroblastoma ( )
Osteosarcoma ( )
Prostate cancer ( )
Rhabdomyosarcoma ( )
Dedifferentiated liposarcoma ( )
Nasopharyngeal carcinoma ( )
Plasma cell myeloma ( )
Prostate neoplasm ( )
Recessive X-linked ichthyosis ( )
UniProt ID
SSX2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
8HQY
Pfam ID
PF01352 ; PF09514
Sequence
MNGDDAFARRPTVGAQIPEKIQKAFDDIAKYFSKEEWEKMKASEKIFYVYMKRKYEAMTK
LGFKATLPPFMCNKRAEDFQGNDLDNDPNRGNQVERPQMTFGRLQGISPKIMPKKPAEEG
NDSEEVPEASGPQNDGKELCPPGKPTTSEKIHERSGPKRGEHAWTHRLRERKQLVIYEEI
SDPEEDDE
Function Could act as a modulator of transcription.
Tissue Specificity
Expressed at high level in the testis. Expressed at low level in thyroid. Not detected in tonsil, colon, lung, spleen, prostate, kidney, striated and smooth muscles. Detected in rhabdomyosarcoma and fibrosarcoma cell lines. Not detected in mesenchymal and epithelial cell lines.
KEGG Pathway
Transcriptio.l misregulation in cancer (hsa05202 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of esophagus DISS6G4D Definitive Altered Expression [1]
Esophageal cancer DISGB2VN Definitive Altered Expression [1]
Neoplasm of esophagus DISOLKAQ Definitive Altered Expression [1]
Acute monocytic leukemia DIS28NEL Strong Altered Expression [2]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [2]
Adult lymphoma DISK8IZR Strong Genetic Variation [3]
Benign neoplasm DISDUXAD Strong Biomarker [4]
Breast cancer DIS7DPX1 Strong Altered Expression [5]
Breast carcinoma DIS2UE88 Strong Altered Expression [5]
Chromosomal disorder DISM5BB5 Strong Genetic Variation [6]
Classic Hodgkin lymphoma DISV1LU6 Strong Altered Expression [7]
Colon cancer DISVC52G Strong Biomarker [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [9]
Desmoplastic small round cell tumor DISLI2ME Strong Genetic Variation [10]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [11]
Leiomyosarcoma DIS6COXM Strong Genetic Variation [3]
Leukemia DISNAKFL Strong Genetic Variation [3]
Lymphoma DISN6V4S Strong Genetic Variation [3]
Malignant peripheral nerve sheath tumor DIS0JTN6 Strong Genetic Variation [12]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [13]
Melanoma DIS1RRCY Strong Altered Expression [14]
Melorheostosis DISIMCL3 Strong Biomarker [15]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [16]
Metastatic prostate carcinoma DISVBEZ9 Strong Altered Expression [17]
Pediatric lymphoma DIS51BK2 Strong Genetic Variation [3]
Prostate carcinoma DISMJPLE Strong Altered Expression [18]
Sarcoma DISZDG3U Strong Biomarker [13]
Seminoma DIS3J8LJ Strong Altered Expression [19]
Soft tissue neoplasm DISP2OHE Strong Genetic Variation [20]
Soft tissue sarcoma DISSN8XB Strong Biomarker [21]
Testicular cancer DIS6HNYO Strong Biomarker [22]
Thyroid cancer DIS3VLDH Strong Altered Expression [3]
Thyroid gland carcinoma DISMNGZ0 Strong Altered Expression [3]
Bone osteosarcoma DIST1004 moderate Altered Expression [14]
Neuroblastoma DISVZBI4 moderate Biomarker [23]
Osteosarcoma DISLQ7E2 moderate Altered Expression [14]
Prostate cancer DISF190Y moderate Altered Expression [18]
Rhabdomyosarcoma DISNR7MS moderate Biomarker [24]
Dedifferentiated liposarcoma DISYJUCJ Limited Genetic Variation [4]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [25]
Plasma cell myeloma DIS0DFZ0 Limited Altered Expression [26]
Prostate neoplasm DISHDKGQ Limited Biomarker [17]
Recessive X-linked ichthyosis DISZY56W Limited Biomarker [4]
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⏷ Show the Full List of 43 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 SSX2 (SSX2). [27]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Protein SSX2 (SSX2). [28]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Protein SSX2 (SSX2). [28]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Protein SSX2 (SSX2). [29]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Protein SSX2 (SSX2). [30]
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References

1 Heterogeneous expression of GAGE, NY-ESO-1, MAGE-A and SSX proteins in esophageal cancer: Implications for immunotherapy.Int J Cancer. 2006 Jan 1;118(1):123-8. doi: 10.1002/ijc.21219.
2 Targeting the arginine metabolic brake enhances immunotherapy for leukaemia.Int J Cancer. 2019 Oct 15;145(8):2201-2208. doi: 10.1002/ijc.32028. Epub 2019 Jan 11.
3 Expression of SSX genes in human tumors.Int J Cancer. 1998 Jul 3;77(1):19-23. doi: 10.1002/(sici)1097-0215(19980703)77:1<19::aid-ijc4>3.0.co;2-2.
4 Molecular analyses in the diagnosis and prediction of prognosis in non-GIST soft tissue sarcomas: A systematic review and meta-analysis.Cancer Treat Rev. 2018 May;66:74-81. doi: 10.1016/j.ctrv.2018.04.005. Epub 2018 Apr 22.
5 Ectopic expression of cancer/testis antigen SSX2 induces DNA damage and promotes genomic instability.Mol Oncol. 2015 Feb;9(2):437-49. doi: 10.1016/j.molonc.2014.09.001. Epub 2014 Oct 6.
6 Diagnosis of synovial sarcoma with the reverse transcriptase-polymerase chain reaction: analyses of 84 soft tissue and bone tumors.Diagn Mol Pathol. 1998 Apr;7(2):102-10. doi: 10.1097/00019606-199804000-00007.
7 Expression of SSX genes in the neoplastic cells of Hodgkin's lymphoma.Hum Pathol. 2002 May;33(5):496-502. doi: 10.1053/hupa.2002.124909.
8 The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40.Cancer Res. 1996 Oct 15;56(20):4766-72.
9 Molecular and immunological evaluation of the expression of cancer/testis gene products in human colorectal cancer.Cancer Immunol Immunother. 2007 Jun;56(6):839-47. doi: 10.1007/s00262-006-0228-5. Epub 2006 Sep 8.
10 Defining Ewing and Ewing-like small round cell tumors (SRCT): The need for molecular techniques in their categorization and differential diagnosis. A study of 200 cases.Ann Diagn Pathol. 2016 Jun;22:25-32. doi: 10.1016/j.anndiagpath.2016.03.002. Epub 2016 Mar 14.
11 Expression of cancer-testis antigen (CTA) in tumor tissues and peripheral blood of Chinese patients with hepatocellular carcinoma.Life Sci. 2006 Jul 17;79(8):744-8. doi: 10.1016/j.lfs.2006.02.024. Epub 2006 Feb 28.
12 Lack of SYT-SSX fusion transcripts in malignant peripheral nerve sheath tumors on RT-PCR analysis of 34 archival cases.Lab Invest. 2002 May;82(5):609-18. doi: 10.1038/labinvest.3780455.
13 Evaluation of expression of cancer stem cell markers and fusion gene in synovial sarcoma: Insights into histogenesis and pathogenesis.Oncol Rep. 2017 Jun;37(6):3351-3360. doi: 10.3892/or.2017.5617. Epub 2017 May 2.
14 Oncogenic functions of the cancer-testis antigen SSX on the proliferation, survival, and signaling pathways of cancer cells.PLoS One. 2014 Apr 30;9(4):e95136. doi: 10.1371/journal.pone.0095136. eCollection 2014.
15 A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening.Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1914-8. doi: 10.1073/pnas.94.5.1914.
16 Cancer/testis antigen expression in human mesenchymal stem cells: down-regulation of SSX impairs cell migration and matrix metalloproteinase 2 expression.Cancer Res. 2005 Mar 15;65(6):2207-15. doi: 10.1158/0008-5472.CAN-04-1882.
17 Inducible expression of a prostate cancer-testis antigen, SSX-2, following treatment with a DNA methylation inhibitor.Prostate. 2007 Dec 1;67(16):1781-90. doi: 10.1002/pros.20665.
18 Inducible expression of cancer-testis antigens in human prostate cancer.Oncotarget. 2016 Dec 20;7(51):84359-84374. doi: 10.18632/oncotarget.12711.
19 Chromosome X-encoded cancer/testis antigens show distinctive expression patterns in developing gonads and in testicular seminoma.Hum Reprod. 2011 Dec;26(12):3232-43. doi: 10.1093/humrep/der330. Epub 2011 Oct 20.
20 The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the nucleus and associates with it in an active complex.Oncogene. 2006 Jun 22;25(26):3661-9. doi: 10.1038/sj.onc.1209413. Epub 2006 Feb 6.
21 A novel sarcoma with dual differentiation: clinicopathologic and molecular characterization of a combined synovial sarcoma and extraskeletal myxoid chondrosarcoma.Am J Surg Pathol. 2012 Jul;36(7):1093-8. doi: 10.1097/PAS.0b013e31824cd174.
22 A peptide epitope derived from the cancer testis antigen HOM-MEL-40/SSX2 capable of inducing CD4?and CD8?T-cell as well as B-cell responses.Cancer Immunol Immunother. 2011 Sep;60(9):1333-46. doi: 10.1007/s00262-011-1030-6. Epub 2011 Jun 1.
23 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.
24 Differentiating Ewing's sarcoma from other round blue cell tumors using a RT-PCR translocation panel on formalin-fixed paraffin-embedded tissues.Mod Pathol. 2007 Mar;20(3):397-404. doi: 10.1038/modpathol.3800755.
25 Human Leukocyte Antigen-A Allele Distribution in Nasopharyngeal Carcinoma Patients Showing Anti-Melanoma-Associated Antigen A or Synovial Sarcoma X-2 T Cell Response in Blood.Chin Med J (Engl). 2018 Jun 5;131(11):1289-1295. doi: 10.4103/0366-6999.232791.
26 The clinical value of the quantitative detection of four cancer-testis antigen genes in multiple myeloma.Mol Cancer. 2014 Feb 5;13:25. doi: 10.1186/1476-4598-13-25.
27 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.
28 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
29 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.
30 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.