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Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay.

ABSTRACT: 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.

SUBMITTER: Laporte AN

PROVIDER: S-EPMC5085163 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay.

Laporte Aimée N AN Ji Jennifer X JX Ma Limin L Nielsen Torsten O TO Brodin Bertha A BA

Oncotarget 20160601 23

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 ...[more]

PMID: 27120803

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