PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells

Monika Raab, Mourad Sanhaji, Yves Matthess, Albrecht Hörlin, Ioana Lorenz, Christina Dötsch, Nils Habbe, Oliver Waidmann, Elisabeth Kurunci-Csacsko, Ron Firestein, Sven Becker and Klaus Strebhardt ()
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Monika Raab: Goethe-University
Mourad Sanhaji: Goethe-University
Yves Matthess: Goethe-University
Albrecht Hörlin: Goethe-University
Ioana Lorenz: Goethe-University
Christina Dötsch: Goethe-University
Nils Habbe: Goethe-University
Oliver Waidmann: Goethe-University
Elisabeth Kurunci-Csacsko: Goethe-University
Ron Firestein: Centre for Cancer Research, Hudson Institute of Medical Research
Sven Becker: Goethe-University
Klaus Strebhardt: Goethe-University

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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 Min/+ mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly.

Date: 2018
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DOI: 10.1038/s41467-018-03494-4

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