Targeting intrinsically disordered nuclear protein 1 (NUPR1) with single-domain antibodies alleviates triple-negative breast cancer (TNBC) progression in vivo.

ABSTRACT: Triple-negative breast cancer (TNBC) is a highly aggressive subtype that currently lacks effective targeted therapies. Transcriptional co-regulator nuclear protein 1 (NUPR1) has been identified as a key stress-adaptive disordered protein that promotes tumor progression and therapy-induced resistance. In this study, we developed a robust high-throughput platform integrating in situ proximity ligation assay followed by DNA sequencing (isPLA-seq), NanoBiT assays, and C-degron degradation validation to screen for functional single-domain antibodies (sdAbs) targeting NUPR1. Consequently, sdAb#07.81 emerged as a lead candidate, demonstrating strong binding affinity and the ability to degrade endogenous NUPR1 in TNBC cells. Functional assays confirmed that sdAb#07.81 suppressed TNBC cell growth,

SUBMITTER: Wang T 

PROVIDER: S-EPMC12748981 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature