Ferroptosis has emerged as an attractive strategy in cancer therapy. Understanding the operational networks regulating ferroptosis may unravel vulnerabilities that could be harnessed for therapeutic benefit. Using CRISPR-activation screens in ferroptosis hypersensitive cells, we identify the selenoprotein P (SELENOP) receptor, LRP8, as a key determinant protecting MYCN-amplified neuroblastoma cells from ferroptosis. Genetic deletion of LRP8 leads to ferroptosis as a result of an insufficient supply of selenocysteine, which is required for the translation of the antiferroptotic selenoprotein GPX4. This dependency is caused by low expression of alternative selenium uptake pathways such as system Xc- . The identification of LRP8 as a specific vulnerability of MYCN-amplified neuroblastoma cells was confirmed in constitutive and inducible LRP8 knockout orthotopic xenografts. These findings disclose a yet-unaccounted mechanism of selective ferroptosis induction that might be explored as a therapeutic strategy for high-risk neuroblastoma and potentially other MYCN-amplified entities.
Pharmacology, Toxicology and Pharmaceutical Science
2
3%
Mathematics
1
2%
Immunology and Microbiology
1
2%
Medicine and Dentistry
1
2%
Other
1
2%
Unknown
39
62%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 16. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 July 2023.
All research outputs
#2,483,227
of 27,509,154 outputs
Outputs from EMBO Molecular Medicine
#535
of 1,758 outputs
Outputs of similar age
#43,281
of 378,569 outputs
Outputs of similar age from EMBO Molecular Medicine
#10
of 26 outputs
Altmetric has tracked 27,509,154 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,758 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.9. This one has gotten more attention than average, scoring higher than 69% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 378,569 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.
