Open AccessIdentification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay
Author(s) -
Aimée N. Laporte,
Jennifer X. Ji,
Limin Ma,
Torsten O. Nielsen,
Bertha Brodin
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.8882
Subject(s) - proximity ligation assay , synovial sarcoma , ligation , cancer research , cytotoxic t cell , effector , sarcoma , fusion protein , medicine , doxorubicin , drug discovery , biology , immunology , bioinformatics , receptor , pathology , microbiology and biotechnology , in vitro , chemotherapy , biochemistry , gene , recombinant dna
Conventional cytotoxic therapies for synovial sarcoma provide limited benefit. Drugs specifically targeting the product of its driver translocation are currently unavailable, in part because the SS18-SSX oncoprotein functions via aberrant interactions within multiprotein complexes. Proximity ligation assay is a recently-developed method that assesses protein-protein interactions in situ. Here we report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known.