Synthetic lethality between the cohesin subunits <i>STAG1</i> and <i>STAG2</i> in diverse cancer contexts.

ABSTRACT: Recent genome analyses have identified recurrent mutations in the cohesin complex in a wide range of human cancers. Here we demonstrate that the most frequently mutated subunit of the cohesin complex, STAG2, displays a strong synthetic lethal interaction with its paralog STAG1. Mechanistically, STAG1 loss abrogates sister chromatid cohesion in STAG2 mutated but not in wild-type cells leading to mitotic catastrophe, defective cell division and apoptosis. STAG1 inactivation inhibits the proliferation of STAG2 mutated but not wild-type bladder cancer and Ewing sarcoma cell lines. Restoration of STAG2 expression in a mutated bladder cancer model alleviates the dependency on STAG1. Thus, STAG1 and STAG2 support sister chromatid cohesion to redundantly ensure cell survival.

SUBMITTER: van der Lelij P 

PROVIDER: S-EPMC5531830 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature