UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease.

ABSTRACT:

Background

Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies.

Methods

Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins.

Results

Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual P

SUBMITTER: Paisana E 

PROVIDER: S-EPMC10195208 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature