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

Author

Listed:
  • Monika Raab

    (Goethe-University)

  • Mourad Sanhaji

    (Goethe-University)

  • Yves Matthess

    (Goethe-University
    German Cancer Consortium (DKTK)/ German Cancer Research Center)

  • 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
    Monash University)

  • Sven Becker

    (Goethe-University)

  • Klaus Strebhardt

    (Goethe-University
    German Cancer Consortium (DKTK)/ German Cancer Research Center)

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.

Suggested Citation

  • Monika Raab & Mourad Sanhaji & Yves Matthess & Albrecht Hörlin & Ioana Lorenz & Christina Dötsch & Nils Habbe & Oliver Waidmann & Elisabeth Kurunci-Csacsko & Ron Firestein & Sven Becker & Klaus Strebh, 2018. "PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03494-4
    DOI: 10.1038/s41467-018-03494-4
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