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@ARTICLE{Haas:304085,
author = {A. Haas and F. Wenz and J. Hattemer and J. Wesslowski and
G. Davidson and O. Voloshanenko$^*$ and M. Boutros$^*$ and
S. P. Acebron and H. Bastians},
title = {{W}nt10b signaling regulates replication stress-induced
chromosomal instability in human cancer.},
journal = {Life science alliance},
volume = {8},
number = {11},
issn = {2575-1077},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DKFZ-2025-01753},
pages = {e202503295},
year = {2025},
abstract = {Wnt signaling pathways are involved in various
developmental and tissue maintenance functions, whereas
deregulated Wnt signaling is closely linked to human cancer.
Recent work revealed that loss of Wnt signaling impairs
mitosis and causes abnormal microtubule growth at the
mitotic spindle resulting in chromosome missegregation and
aneuploidy, both of which are hallmarks of cancer cells
exhibiting chromosomal instability (CIN). Here, we show that
upon DNA replication stress, a condition typically
associated with CIN, Wnt10b acts to prevent increased
microtubule dynamics from the S phase until mitosis, thereby
ensuring faithful chromosome segregation. Interestingly,
replication stress-induced chromosomal breaks are also
efficiently suppressed by Wnt10b. Thus, our results show
that Wnt10b signaling regulates replication stress-induced
chromosome missegregation and breakage, and hence is a
determinant for broad genome instability in cancer cells.},
keywords = {Humans / Chromosomal Instability: genetics / DNA
Replication: genetics / Neoplasms: genetics / Neoplasms:
metabolism / Wnt Proteins: metabolism / Wnt Proteins:
genetics / Mitosis: genetics / Cell Line, Tumor / Chromosome
Segregation: genetics / Wnt Signaling Pathway: genetics /
Microtubules: metabolism / Genomic Instability / Signal
Transduction / Proto-Oncogene Proteins / Wnt Proteins (NLM
Chemicals) / WNT10B protein, human (NLM Chemicals) /
Proto-Oncogene Proteins (NLM Chemicals)},
cin = {B110},
ddc = {570},
cid = {I:(DE-He78)B110-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40846632},
doi = {10.26508/lsa.202503295},
url = {https://inrepo02.dkfz.de/record/304085},
}