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000304085 041__ $$aEnglish
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000304085 1001_ $$aHaas, Alexander$$b0
000304085 245__ $$aWnt10b signaling regulates replication stress-induced chromosomal instability in human cancer.
000304085 260__ $$aHeidelberg$$bEMBO Press$$c2025
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000304085 520__ $$aWnt 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.
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000304085 650_7 $$2NLM Chemicals$$aWnt Proteins
000304085 650_7 $$2NLM Chemicals$$aWNT10B protein, human
000304085 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins
000304085 650_2 $$2MeSH$$aHumans
000304085 650_2 $$2MeSH$$aChromosomal Instability: genetics
000304085 650_2 $$2MeSH$$aDNA Replication: genetics
000304085 650_2 $$2MeSH$$aNeoplasms: genetics
000304085 650_2 $$2MeSH$$aNeoplasms: metabolism
000304085 650_2 $$2MeSH$$aWnt Proteins: metabolism
000304085 650_2 $$2MeSH$$aWnt Proteins: genetics
000304085 650_2 $$2MeSH$$aMitosis: genetics
000304085 650_2 $$2MeSH$$aCell Line, Tumor
000304085 650_2 $$2MeSH$$aChromosome Segregation: genetics
000304085 650_2 $$2MeSH$$aWnt Signaling Pathway: genetics
000304085 650_2 $$2MeSH$$aMicrotubules: metabolism
000304085 650_2 $$2MeSH$$aGenomic Instability
000304085 650_2 $$2MeSH$$aSignal Transduction
000304085 650_2 $$2MeSH$$aProto-Oncogene Proteins
000304085 7001_ $$00009-0003-0114-2772$$aWenz, Friederike$$b1
000304085 7001_ $$aHattemer, Janina$$b2
000304085 7001_ $$00000-0003-3674-1372$$aWesslowski, Janine$$b3
000304085 7001_ $$00000-0002-2264-5518$$aDavidson, Gary$$b4
000304085 7001_ $$0P:(DE-He78)ad64f12d9ccfe830ecddc2fe9635c569$$aVoloshanenko, Oksana$$b5$$udkfz
000304085 7001_ $$0P:(DE-He78)3c0da8e3caa2aa50cad85152aa0465ad$$aBoutros, Michael$$b6$$udkfz
000304085 7001_ $$aAcebron, Sergio P$$b7
000304085 7001_ $$00000-0001-7915-3648$$aBastians, Holger$$b8
000304085 773__ $$0PERI:(DE-600)2948687-7$$a10.26508/lsa.202503295$$gVol. 8, no. 11, p. e202503295 -$$n11$$pe202503295$$tLife science alliance$$v8$$x2575-1077$$y2025
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