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@ARTICLE{Myacheva:182135,
author = {K. Myacheva$^*$ and A. Walsh and M. Riester$^*$ and G.
Pelos$^*$ and J. Carl$^*$ and S. Diederichs$^*$},
title = {{CRISPR}i screening identifies {CASP}8{AP}2 as an essential
viability factor in lung cancer controlling tumor cell death
via the {AP}-1 pathway.},
journal = {Cancer letters},
volume = {552},
number = {1},
issn = {0304-3835},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2022-02452},
pages = {215958},
year = {2023},
note = {#EA:B150#LA:B150# / 2023 Jan 1;552:215958},
abstract = {Since lung cancer remains the leading cause of cancer death
globally, there is an urgent demand for novel therapeutic
targets. We carried out a CRISPR interference (CRISPRi)
loss-of-function screen for human lung adenocarcinoma (LUAD)
targeting 2098 deregulated genes using a customized
algorithm to comprehensively probe the functionality of
every resolvable transcriptional start site (TSS). CASP8AP2
was identified as the only hit that significantly affected
the viability of all eight screened LUAD cell lines while
the viability of non-transformed lung cells was only
moderately impacted. Knockdown (KD) of CASP8AP2 induced both
autophagy and apoptotic cell death pathways. Systematic
expression profiling linked the AP-1 transcription factor to
the CASP8AP2 KD-induced cancer cell death. Furthermore,
inhibition of AP-1 reverted the CASP8AP2 silencing-induced
phenotype. Overall, the tailored CRISPRi screen profiled the
impact of over 2000 genes on the survival of eight LUAD cell
lines and identified the CASP8AP2 - AP-1 axis mediating lung
cancer viability.},
keywords = {Autophagy (Other) / CRISPR (Other) / Caspase (Other) /
FLASH (Other) / Lung adenocarcinoma (Other) / NSCLC (Other)},
cin = {B150 / FR01},
ddc = {570},
cid = {I:(DE-He78)B150-20160331 / I:(DE-He78)FR01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36252816},
doi = {10.1016/j.canlet.2022.215958},
url = {https://inrepo02.dkfz.de/record/182135},
}