Protein Aggregation Patterns Inform about Breast Cancer Response to Antiestrogens and Reveal the RNA Ligase RTCB as Mediator of Acquired Tamoxifen Resistance.

ABSTRACT: The protein quality control network, including autophagy, the proteasome and the unfolded protein response (UPR), is triggered by stress and is overactive in acquired antiestrogen therapy resistance. We show for the first time that the aggresome load correlates with apoptosis and is increased in antiestrogen-sensitive cells compared to endocrine-resistant variants. LC-MS/MS analysis of the aggregated proteins obtained after 4OH-tamoxifen and Fulvestrant treatment identified proteins with essential function in protein quality control in antiestrogen-sensitive cells, but not in resistant variants. These include the UPR modulators RTCB and PDIA6, as well as many proteasome proteins such as PSMC2 and PSMD11. RTCB is a tRNA and XBP1 ligase and its aggregation induced by antiestrogens correlated

SUBMITTER: Direito I 

PROVIDER: S-EPMC8269126 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature