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@ARTICLE{Alborzinia:277470,
author = {H. Alborzinia$^*$ and Z. Chen and U. Yildiz$^*$ and F. P.
Freitas and F. C. E. Vogel$^*$ and J. P. Varga$^*$ and J.
Batani and C. Bartenhagen and W. Schmitz and G. Büchel and
B. Michalke and J. Zheng and S. Meierjohann and E. Girardi
and E. Espinet and A. F. Flórez and A. F. Dos Santos and N.
Aroua$^*$ and T. Cheytan$^*$ and J. Haenlin$^*$ and L.
Schlicker$^*$ and T. N. Xavier da Silva$^*$ and A.
Przybylla$^*$ and P. Zeisberger$^*$ and G. Superti-Furga and
M. Eilers and M. Conrad and M. Fabiano and U. Schweizer and
M. Fischer and A. Schulze$^*$ and A. Trumpp$^*$ and J. P.
Friedmann Angeli},
title = {{LRP}8-mediated selenocysteine uptake is a targetable
vulnerability in {MYCN}-amplified neuroblastoma.},
journal = {EMBO molecular medicine},
volume = {15},
number = {8},
issn = {1757-4676},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DKFZ-2023-01391},
pages = {e18014},
year = {2023},
note = {#EA:A010#LA:A010# / 2023 Aug 7;15(8):e18014},
abstract = {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.},
keywords = {ferroptosis (Other) / neuroblastoma (Other) /
selenocysteine (Other) / selenoprotein (Other) / synthetic
lethality (Other)},
cin = {A010 / A410},
ddc = {610},
cid = {I:(DE-He78)A010-20160331 / I:(DE-He78)A410-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37435859},
doi = {10.15252/emmm.202318014},
url = {https://inrepo02.dkfz.de/record/277470},
}