TY  - JOUR
AU  - Zuidhof, Hidde R
AU  - Müller, Christine
AU  - Kortman, Gertrud
AU  - Wardenaar, René
AU  - Stepanova, Ekaterina
AU  - Loayza-Puch, Fabricio
AU  - Calkhoven, Cornelis F
TI  - The m6A demethylase FTO promotes C/EBPβ-LIP translation to perform oncogenic functions in breast cancer cells.
JO  - The FEBS journal
VL  - 292
IS  - 10
SN  - 0014-2956
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2025-00462
SP  - 2688-2709
PY  - 2025
N1  - 2025 May;292(10):2688-2709
AB  - 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.
KW  - C/EBPβ (Other)
KW  - FTO (Other)
KW  - breast cancer (Other)
KW  - mRNA translation (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40022434
DO  - DOI:DOI:10.1111/febs.70033
UR  - https://inrepo02.dkfz.de/record/299504
ER  -