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@ARTICLE{MonfortVengut:298228,
author = {A. Monfort-Vengut and N. Sanz-Gómez and S.
Ballesteros-Sánchez and B. Ortigosa and A. Cambón and M.
Ramos$^*$ and Á. M. Lorenzo and M. Escribano-Cebrián and
J. M. Rosa-Rosa and J. Martínez-López and R.
Sánchez-Prieto and R. Sotillo$^*$ and G. de Cárcer},
title = {{O}smotic stress influences microtubule drug response via
{WNK}1 kinase signaling.},
journal = {Drug resistance updates},
volume = {79},
issn = {1368-7646},
address = {Oxford},
publisher = {Elsevier},
reportid = {DKFZ-2025-00235},
pages = {101203},
year = {2025},
abstract = {Ion homeostasis is critical for numerous cellular
processes, and disturbances in ionic balance underlie
diverse pathological conditions, including cancer
progression. Targeting ion homeostasis is even considered as
a strategy to treat cancer. However, very little is known
about how ion homeostasis may influence anticancer drug
response. In a genome-wide CRISPR-Cas9 resistance drug
screen, we identified and validated the master osmostress
regulator WNK1 kinase as a modulator of the response to the
mitotic inhibitor rigosertib. Osmotic stress and WNK1
inactivation lead to an altered response not only to
rigosertib treatment but also to other microtubule-related
drugs, minimizing the prototypical mitotic arrest produced
by these compounds. This effect is due to an alteration in
microtubule stability and polymerization dynamics, likely
maintained by fluctuations in intracellular molecular
crowding upon WNK1 inactivation. This promotes resistance to
microtubule depolymerizing compounds, and increased
sensitivity to microtubule stabilizing drugs. In summary,
our data proposes WNK1 osmoregulation activity as an
important modulator for microtubule-associated chemotherapy
response.},
keywords = {Microtubule dynamics (Other) / Mitosis (Other) / Osmotic
stress (Other) / Rigosertib (Other) / WNK1 (Other)},
cin = {B220},
ddc = {610},
cid = {I:(DE-He78)B220-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39855050},
doi = {10.1016/j.drup.2025.101203},
url = {https://inrepo02.dkfz.de/record/298228},
}