In:
EMBO Molecular Medicine, EMBO, Vol. 15, No. 8 ( 2023-08-07)
Abstract:
image The low‐density lipoprotein receptor (LRP8) was identified as a critical suppressor of ferroptosis in MYCN‐amplified neuroblastoma. Blocking selenium/selenocysteine uptake mechanisms via LRP8 offers a selective strategy to induce ferroptosis and disrupt GPX4 function. Ferroptosis, a cell death modality, is gaining interest as a therapeutic approach against challenging tumors. GPX4 is crucial for suppressing ferroptosis, but suitable in vivo inhibitors are lacking, limiting translation to cancer therapies. Genome‐wide and single‐cell CRISPR‐activation screens reveal LRP8 as a critical ferroptosis suppressor in MYCN‐amplified neuroblastoma. Blocking selenium/selenocysteine uptake via LRP8 disrupts GPX4 function and selectively induces ferroptotic cell death. LRP8 dependency emerges as the result of the low system Xc − activity suggesting that targeting LRP8 could be explore in other entities such as AML and lymphoma.
Type of Medium:
Online Resource
ISSN:
1757-4676
,
1757-4684
DOI:
10.15252/emmm.202318014
Language:
English
Publisher:
EMBO
Publication Date:
2023
detail.hit.zdb_id:
2485479-7
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