Back to Search
Start Over
Wnt10b-GSK3β–dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells
- Source :
- Life Science Alliance
- Publication Year :
- 2020
- Publisher :
- Life Science Alliance, LLC, 2020.
-
Abstract
- Autocrine Wnt10b signaling ensures proper mitotic microtubule polymerization and faithful chromosome segregation.<br />Wnt signaling is crucial for proper development, tissue homeostasis and cell cycle regulation. A key role of Wnt signaling is the GSK3β-mediated stabilization of β-catenin, which mediates many of the critical roles of Wnt signaling. In addition, it was recently revealed that Wnt signaling can also act independently of β-catenin. In fact, Wnt mediated stabilization of proteins (Wnt/STOP) that involves an LRP6-DVL–dependent signaling cascade is required for proper regulation of mitosis and for faithful chromosome segregation in human somatic cells. We show that inhibition of Wnt/LRP6 signaling causes whole chromosome missegregation and aneuploidy by triggering abnormally increased microtubule growth rates in mitotic spindles, and this is mediated by increased GSK3β activity. We demonstrate that proper mitosis and maintenance of numerical chromosome stability requires continuous basal autocrine Wnt signaling that involves secretion of Wnts. Importantly, we identified Wnt10b as a Wnt ligand required for the maintenance of normal mitotic microtubule dynamics and for proper chromosome segregation. Thus, a self-maintaining Wnt10b-GSK3β–driven cellular machinery ensures the proper execution of mitosis and karyotype stability in human somatic cells.
- Subjects :
- Somatic cell
Health, Toxicology and Mutagenesis
Dishevelled Proteins
Mitosis
macromolecular substances
Spindle Apparatus
Plant Science
Biology
Transfection
Microtubules
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Receptors, G-Protein-Coupled
Chromosome segregation
03 medical and health sciences
0302 clinical medicine
Chromosomal Instability
Chromosome Segregation
Proto-Oncogene Proteins
Humans
Gene Silencing
Autocrine signalling
Wnt Signaling Pathway
health care economics and organizations
Research Articles
beta Catenin
Tissue homeostasis
030304 developmental biology
0303 health sciences
Glycogen Synthase Kinase 3 beta
Ecology
Protein Stability
technology, industry, and agriculture
Intracellular Signaling Peptides and Proteins
Wnt signaling pathway
LRP6
Cell cycle
Aneuploidy
HCT116 Cells
humanities
Cell biology
Wnt Proteins
Low Density Lipoprotein Receptor-Related Protein-6
Intercellular Signaling Peptides and Proteins
030217 neurology & neurosurgery
Research Article
Subjects
Details
- ISSN :
- 25751077
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Life Science Alliance
- Accession number :
- edsair.doi.dedup.....906c89338d8cf44a04443de1920e8716