RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding.

ABSTRACT:

Background

Ceramide metabolism is crucial in the progress of brain metastasis (BM). However, it remains unexplored whether targeting ceramide metabolism may arrest BM.

Methods

RNA sequencing was applied to screen different genes in primary and metastatic foci and whole-exome sequencing (WES) to seek crucial abnormal pathway in BM + and BM-patients. Cellular arrays were applied to analyze the permeability of blood-brain barrier (BBB) and the activation or inhibition of pathway. Database and Co-Immunoprecipitation (Co-IP) assay were adopted to verify the protein-protein interaction. Xenograft and zebrafish model were further employed to verify the cellular results.

Results

RNA sequencing and WES reported the involvement of RPTOR and ceramide metabolism in BM progress. R

SUBMITTER: Lin Y 

PROVIDER: S-EPMC10759737 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature