Project Summary

Chromosomal instability (CIN) associated with high-grade aneuploidy is a major characteristic of human cancer and can contribute to tumorigenesis and tumor progression. However, the molecular mechanisms and genetic lesions causing CIN are largely unknown.

 

We have recently uncovered that the CHK2-BRCA1 tumor suppressor pathway is required for the maintenance of chromosomal stability in human somatic cells. In addition to that, our preliminary results showed that inappropriate Wnt signaling causes aneuploidy, which supports the emerging role of the Wnt pathway as a key regulator of mitosis, chromosome segregation and chromosomal stability.

 

We are aiming to investigate the role of Wnt signaling in mitosis and for the maintenance of chromosomal stability in detail. By using live-cell microscopy combined with loss- and gain-of-function studies we will investigate whether silencing or activating the Wnt signaling pathway is associated with abnormal mitotic progression and defects in chromosome segregation. Our work will reveal whether cancer associated abnormal Wnt signaling or particular components of the Wnt signaling pathway are involved in the mechanisms of tumorigenesis and tumor progression via the induction of chromosomal instability and aneuploidy.