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Wnt10b-GSK3β-dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells

Yu-Chih Lin1, Alexander Haas1, Anja Bufe2

  • 1Georg-August University Göttingen, Göttingen Center for Molecular Biosciences (GZMB) and University Medical Center Göttingen (UMG), Institute of Molecular Oncology, Section for Cellular Oncology, Göttingen, Germany.

Life Science Alliance
|December 1, 2020
PubMed

Insights

Wnt signaling, independent of beta-catenin, regulates mitosis and chromosome stability. Wnt10b and GSK3β are crucial for accurate cell division and karyotype integrity in human cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Wnt signaling is vital for development and homeostasis.
  • It regulates cell cycle via GSK3β-mediated β-catenin stabilization.
  • Wnt signaling also acts independently of β-catenin through Wnt/STOP pathways.

Purpose of the Study:

  • To investigate the role of Wnt/STOP signaling in mitosis and chromosome segregation.
  • To identify specific Wnt ligands involved in maintaining mitotic fidelity.
  • To elucidate the mechanism by which Wnt signaling impacts microtubule dynamics and chromosome stability.

Main Methods:

  • Inhibition of Wnt/LRP6 signaling.
  • Analysis of chromosome missegregation and aneuploidy.
  • Measurement of microtubule growth rates in mitotic spindles.
  • Assessment of GSK3β activity.
  • Identification of Wnt ligands using molecular biology techniques.

Main Results:

  • Inhibition of Wnt/LRP6 signaling led to chromosome missegregation and aneuploidy.
  • This was caused by increased microtubule growth rates mediated by elevated GSK3β activity.
  • Continuous basal autocrine Wnt signaling is essential for mitotic fidelity.
  • Wnt10b was identified as a key Wnt ligand for mitotic microtubule dynamics and chromosome segregation.

Conclusions:

  • A Wnt10b-GSK3β signaling axis ensures proper mitosis and karyotype stability in human somatic cells.
  • This Wnt-driven machinery maintains numerical chromosome stability during cell division.
  • Wnt signaling, independent of β-catenin, plays a critical role in ensuring faithful chromosome segregation.

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