A novel small-molecule antagonizes PRMT5-mediated KLF4 methylation for targeted therapy.

ABSTRACT:

Background

Triple negative breast cancers (TNBCs) have a poor prognosis and are not amenable to endocrine- or HER2-targeted therapies. The malignant and invasive feature of TNBCs is correlated with its high cancer stem cell population. Recent results from us and others have unveiled an oncogenic role for the PRMT5-KLF4 axis in regulating tumor progression by orchestrating the stemness in mammary tumor cell as well as genome stability. Methylation of KLF4 by PRMT5 leads to KLF4 stabilization, resulting in promoting mitogenesis.

Methods

We have developed a small molecule inhibitor, WX2-43, that specifically intercepts the interaction between PRMT5 and KLF4, thereby enhancing KLF4 degradation.

Findings

Results from our characterization demonstrate that WX2-43 binds to th

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC6604046 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature