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000298228 1001_ $$aMonfort-Vengut, Ana$$b0
000298228 245__ $$aOsmotic stress influences microtubule drug response via WNK1 kinase signaling.
000298228 260__ $$aOxford$$bElsevier$$c2025
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000298228 520__ $$aIon homeostasis is critical for numerous cellular processes, and disturbances in ionic balance underlie diverse pathological conditions, including cancer progression. Targeting ion homeostasis is even considered as a strategy to treat cancer. However, very little is known about how ion homeostasis may influence anticancer drug response. In a genome-wide CRISPR-Cas9 resistance drug screen, we identified and validated the master osmostress regulator WNK1 kinase as a modulator of the response to the mitotic inhibitor rigosertib. Osmotic stress and WNK1 inactivation lead to an altered response not only to rigosertib treatment but also to other microtubule-related drugs, minimizing the prototypical mitotic arrest produced by these compounds. This effect is due to an alteration in microtubule stability and polymerization dynamics, likely maintained by fluctuations in intracellular molecular crowding upon WNK1 inactivation. This promotes resistance to microtubule depolymerizing compounds, and increased sensitivity to microtubule stabilizing drugs. In summary, our data proposes WNK1 osmoregulation activity as an important modulator for microtubule-associated chemotherapy response.
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000298228 650_7 $$2Other$$aMicrotubule dynamics
000298228 650_7 $$2Other$$aMitosis
000298228 650_7 $$2Other$$aOsmotic stress
000298228 650_7 $$2Other$$aRigosertib
000298228 650_7 $$2Other$$aWNK1
000298228 7001_ $$aSanz-Gómez, Natalia$$b1
000298228 7001_ $$aBallesteros-Sánchez, Sandra$$b2
000298228 7001_ $$aOrtigosa, Beatriz$$b3
000298228 7001_ $$aCambón, Aitana$$b4
000298228 7001_ $$0P:(DE-HGF)0$$aRamos, Maria$$b5
000298228 7001_ $$aLorenzo, Ángela Montes-San$$b6
000298228 7001_ $$aEscribano-Cebrián, María$$b7
000298228 7001_ $$aRosa-Rosa, Juan Manuel$$b8
000298228 7001_ $$aMartínez-López, Joaquín$$b9
000298228 7001_ $$aSánchez-Prieto, Ricardo$$b10
000298228 7001_ $$0P:(DE-HGF)0$$aSotillo, Rocío$$b11
000298228 7001_ $$ade Cárcer, Guillermo$$b12
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