FGD3 mediates lytic cell death, enhancing efficacy and immunogenicity of chemotherapy agents in breast cancer.

ABSTRACT:

Background

Although anticancer therapies inducing necrosis, necroptosis and pyroptosis trigger cell swelling, plasma membrane rupture (PMR) and release of damage-associated molecular patterns (DAMPs), potentially facilitating antitumor immunity, little was known of proteins and mechanisms controlling the life-death decision of whether swollen and stressed cancer cells enter PMR and undergo lytic cell death.

Methods

We conducted a genome-wide CRISPR screen with selection against a lytic cell death inducer, complemented by studies using breast cancer cells in 2D culture, patient-derived organoids and orthotopic mouse xenografts. The effect of FGD3 on immunogenicity was explored by immunoblotting, immunofluorescence staining and NK-cell mediated cytotoxicity assays. The correla

SUBMITTER: Zhu J 

PROVIDER: S-EPMC12613929 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature