Pharmacological CLK inhibition disrupts SR protein function and RNA splicing blocking cell growth and migration in TNBC.

ABSTRACT:

Background

Dysregulation of alternative splicing plays a pivotal role in tumorigenesis and metastasis in triple-negative breast cancer (TNBC). Serine/arginine-rich (SR) proteins, essential components of the spliceosome, undergo phosphorylation by Cdc2-like kinase (CLK). Here we explored the impact of pharmacological inhibition of CLK using a novel inhibitor, T-025, on the spliceosome complex and transcriptional responses in relation to cell proliferation and migration in TNBC.

Methods

We evaluated the anti-proliferative and anti-migratory efficacy of T-025 in a spectrum of TNBC cell lines. Fluorescent reporter cell lines and flowcytometry were used to determine the effect of T-025 on cell cycle. Deep RNA sequencing was performed to unravel the differentially expressed genes

SUBMITTER: Liu N 

PROVIDER: S-EPMC12309053 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature