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@ARTICLE{Zuidhof:299504,
author = {H. R. Zuidhof and C. Müller and G. Kortman and R.
Wardenaar and E. Stepanova$^*$ and F. Loayza-Puch$^*$ and C.
F. Calkhoven},
title = {{T}he m6{A} demethylase {FTO} promotes {C}/{EBP}β-{LIP}
translation to perform oncogenic functions in breast cancer
cells.},
journal = {The FEBS journal},
volume = {292},
number = {10},
issn = {0014-2956},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2025-00462},
pages = {2688-2709},
year = {2025},
note = {2025 May;292(10):2688-2709},
abstract = {N6-methyladenosine (m6A) is a prevalent posttranscriptional
mRNA modification involved in the regulation of transcript
turnover, translation, and other aspects of RNA fate. The
modification is mediated by multicomponent methyltransferase
complexes (so-called writers) and is reversed through the
action of the m6A-demethylases fat mass and
obesity-associated (FTO) and alkB homolog 5 (ALKBH5)
(so-called erasers). FTO promotes cell proliferation, colony
formation and metastasis in models of triple-negative breast
cancer (TNBC). However, little is known about genome-wide or
specific downstream regulation by FTO. Here, we examined
changes in the genome-wide transcriptome and translatome
following FTO knockdown in TNBC cells. Unexpectedly, FTO
knockdown had a limited effect on the translatome, while
transcriptome analysis revealed that genes related to
extracellular matrix (ECM) and epithelial-mesenchymal
transition (EMT) are regulated through yet unidentified
mechanisms. Differential translation of CEBPB mRNA into the
C/EBPβ transcription factor isoform C/EBPβ-LIP is known to
act in a pro-oncogenic manner in TNBC cells through
regulation of EMT genes. Here we show that FTO is required
for efficient C/EBPβ-LIP expression, suggesting that FTO
has oncogenic functions through regulation of C/EBPβ-LIP.},
keywords = {C/EBPβ (Other) / FTO (Other) / breast cancer (Other) /
mRNA translation (Other)},
cin = {B250},
ddc = {610},
cid = {I:(DE-He78)B250-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40022434},
doi = {DOI:10.1111/febs.70033},
url = {https://inrepo02.dkfz.de/record/299504},
}