PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells
- 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 ApcMin/+ mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly.
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| Author: | Monika Raab, Mourad Sanhaji, Yves Matthess, Albrecht Hörlin, Ioana Lorenz, Christina Dötsch, Nils Habbe, Oliver WaidmannORCiDGND, Elisabeth Kurunci-Csacsko, Ron Firestein, Sven BeckerGND, Klaus StrebhardtORCiD |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-465732 |
| DOI: | https://doi.org/10.1038/s41467-018-03494-4 |
| ISSN: | 2041-1723 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/29549256 |
| Parent Title (English): | Nature Communications |
| Publisher: | Nature Publishing Group UK |
| Place of publication: | [London] |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2018 |
| Date of first Publication: | 2018/03/16 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2018/06/07 |
| Tag: | Cancer; Colon cancer; Gastrointestinal cancer |
| Volume: | 9 |
| Issue: | 1, Art. 1106 |
| Page Number: | 17 |
| First Page: | 1 |
| Last Page: | 17 |
| Note: | Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| HeBIS-PPN: | 433825618 |
| Institutes: | Biowissenschaften / Biowissenschaften |
| Medizin / Medizin | |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
