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@ARTICLE{Teng:301501,
author = {Y.-H. Teng and B. Appiah and G. Andrieux and M. Schrempp
and K. Rose and A. S. Hofmann and M. Ku and S. Beyes and M.
Boerries$^*$ and A. Hecht},
title = {{TGF}-β signaling redirects {S}ox11 gene regulatory
activity to promote partial {EMT} and collective invasion of
oncogenically transformed intestinal organoids.},
journal = {Oncogenesis},
volume = {14},
number = {1},
issn = {2157-9024},
address = {[Erscheinungsort nicht ermittelbar]},
publisher = {Nature Publ.},
reportid = {DKFZ-2025-01040},
pages = {17},
year = {2025},
abstract = {Cancer cells infiltrating surrounding tissue frequently
undergo partial epithelial-mesenchymal transitions (pEMT)
and employ a collective mode of invasion. How these
phenotypic traits are regulated and interconnected remains
underexplored. Here, we used intestinal organoids with
colorectal cancer (CRC) driver mutations as model system to
investigate the mechanistic basis of TGF-β1-induced pEMT
and collective invasion. By scRNA-seq we identified multiple
cell subpopulations representing a broad pEMT spectrum,
where the most advanced pEMT state correlated with the
transcriptional profiles of leader cells in collective
invasion and a poor prognosis mesenchymal subtype of human
CRC. Bioinformatic analyses pinpointed Sox11 as a
transcription factor gene whose expression peaked in the
potential leader/pEMThigh cells. Immunofluorescence staining
confirmed Sox11 expression in cells at the invasive front of
TGF-β1-treated organoids. Loss-of-function and
overexpression experiments showed that Sox11 is necessary,
albeit not sufficient, for TGF-β1-induced pEMT and
collective invasion. In human CRC samples, elevated SOX11
expression was associated with advanced tumor stages and
worse prognosis. Unexpectedly, aside from orchestrating the
organoid response to TGF-β1, Sox11 controlled expression of
genes related to normal gut function and tumor suppression.
Apparently, Sox11 is embedded in several distinct gene
regulatory circuits, contributing to intestinal tissue
homeostasis, tumor suppression, and TGF-β-mediated cancer
cell invasion.},
cin = {FR01},
ddc = {610},
cid = {I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40393982},
doi = {10.1038/s41389-025-00560-7},
url = {https://inrepo02.dkfz.de/record/301501},
}