PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29549256.
- Also identified by DOI 10.1038/s41467-018-03494-4 and PMC identifier 5856809.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities. The inhibition of PLK1 in mitotic, APC-∆C-expressing cells reduces the kinetochore levels of Aurora B and hampers the recruitment of SAC component suggesting a compromised mitotic checkpoint. Furthermore, Plk1 inhibition (RNAi, pharmacological compounds) promotes the development of adenomatous polyps in two independent Apc <sup>Min/+</sup> mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly.
Medical subject headings
- Adenomatous Polyposis Coli
- Adenomatous Polyposis Coli Protein
- Cell Cycle Proteins
- Colonic Neoplasms
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins
- Tumor Suppressor Proteins