ARF4-mediated retrograde trafficking as a driver of chemoresistance in glioblastoma.

ABSTRACT:

Background

Cellular functions hinge on the meticulous orchestration of protein transport, both spatially and temporally. Central to this process is retrograde trafficking, responsible for targeting proteins to the nucleus. Despite its link to many diseases, the implications of retrograde trafficking in glioblastoma (GBM) are still unclear.

Methods

To identify genetic drivers of TMZ resistance, we conducted comprehensive CRISPR-knockout screening, revealing ADP-ribosylation factor 4 (ARF4), a regulator of retrograde trafficking, as a major contributor.

Results

Suppressing ARF4 significantly enhanced TMZ sensitivity in GBM patient-derived xenograft (PDX) models, leading to improved survival rates (P < .01) in both primary and recurrent lines. We also observed that TMZ e

SUBMITTER: Budhiraja S 

PROVIDER: S-EPMC11300013 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature