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@ARTICLE{CidreAranaz:310292,
author = {F. Cidre-Aranaz$^*$ and F. H. Geyer$^*$ and T. Hölting$^*$
and K. M. Hanssen$^*$ and T. Faehling$^*$ and A. Ritter$^*$
and M. Zimmermann$^*$ and L. Mao$^*$ and J. Alonso and A.
Sastre and A. K. Jayavelu$^*$ and M. M. L. Knott$^*$ and J.
Musa$^*$ and T. Grünewald$^*$},
title = {c{IAP}1 inhibitor of apoptosis is a tumor suppressor in
{E}wing sarcoma.},
journal = {Cancer letters},
volume = {nn},
issn = {0304-3835},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2026-00515},
pages = {nn},
year = {2026},
note = {#EA:B410#LA:B410# / epub},
abstract = {Ewing sarcoma (EwS) is a highly aggressive pediatric
malignancy driven by EWSR1::ETS fusion oncoproteins
-primarily EWSR1::FLI1- which deregulate genes essential for
differentiation, proliferation, and cell survival. To
uncover key downstream targets of this fusion involved in
cell differentiation, we combined transcriptomic profiling
of EwS cell lines following EWSR1::FLI1 inhibition with gene
ontology analysis, a clinically annotated gene expression
dataset derived from EwS patient material and network
analyses. This integrative approach identified inhibitor of
apoptosis protein 1 (cIAP1, alias BIRC2) as an
EWSR1::FLI1-suppressed gene. Despite its known oncogenic
role in many cancers, cIAP1 showed minimal expression in
EwS. Using inducible cIAP1 re-expression models in EwS
cells, we demonstrated that cIAP1 re-expression suppresses
proliferation, clonogenic growth, and 3D spheroid formation
in vitro. Transcriptomic and proteomic analyses revealed
that low cIAP1 expression enhances proliferation-related
gene signatures, which are inhibited upon cIAP1
re-expression. In vivo xenograft models revealed that cIAP1
re-expression significantly reduces tumor growth, mitotic
activity, and Ki-67 positivity, while increasing tumor
necrosis and apoptosis. These findings highlight an
unexpected tumor-suppressive role for cIAP1 in fusion-driven
sarcomas, contrasting with its pro-survival function in
other cancers. Collectively, our results identify cIAP1 as a
prognostically relevant, EWSR1::FLI1-regulated hub whose
re-expression disrupts tumor progression, offering a
potential therapeutic strategy to restore tumor-suppressive
pathways in EwS.},
keywords = {BIRC2 (Other) / Ewing sarcoma (Other) / apoptosis (Other) /
cIAP1 (Other) / pediatric sarcoma (Other)},
cin = {B410 / HD01 / A400},
ddc = {570},
cid = {I:(DE-He78)B410-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)A400-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41780845},
doi = {10.1016/j.canlet.2026.218389},
url = {https://inrepo02.dkfz.de/record/310292},
}