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, Klaus Strebhardt

Research output: Contribution to journalArticleResearchpeer-review

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, APCmin/+-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.

Original languageEnglish
Article number1106
Number of pages17
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Cite this

Raab, M., Sanhaji, M., Matthess, Y., Hörlin, A., Lorenz, I., Dötsch, C., ... Strebhardt, K. (2018). PLK1 has tumor-suppressive potential in APC-Truncated colon cancer cells. Nature Communications, 9(1), [1106]. https://doi.org/10.1038/s41467-018-03494-4
Raab, Monika ; Sanhaji, Mourad ; Matthess, Yves ; Hörlin, Albrecht ; Lorenz, Ioana ; Dötsch, Christina ; Habbe, Nils ; Waidmann, Oliver ; Kurunci-Csacsko, Elisabeth ; Firestein, Ron ; Becker, Sven ; Strebhardt, Klaus. / PLK1 has tumor-suppressive potential in APC-Truncated colon cancer cells. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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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, APCmin/+-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.",
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Raab, M, Sanhaji, M, Matthess, Y, Hörlin, A, Lorenz, I, Dötsch, C, Habbe, N, Waidmann, O, Kurunci-Csacsko, E, Firestein, R, Becker, S & Strebhardt, K 2018, 'PLK1 has tumor-suppressive potential in APC-Truncated colon cancer cells' Nature Communications, vol. 9, no. 1, 1106. https://doi.org/10.1038/s41467-018-03494-4

PLK1 has tumor-suppressive potential in APC-Truncated colon cancer cells. / Raab, Monika; Sanhaji, Mourad; Matthess, Yves; Hörlin, Albrecht; Lorenz, Ioana; Dötsch, Christina; Habbe, Nils; Waidmann, Oliver; Kurunci-Csacsko, Elisabeth; Firestein, Ron; Becker, Sven; Strebhardt, Klaus.

In: Nature Communications, Vol. 9, No. 1, 1106, 01.12.2018.

Research output: Contribution to journalArticleResearchpeer-review

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Raab M, Sanhaji M, Matthess Y, Hörlin A, Lorenz I, Dötsch C et al. PLK1 has tumor-suppressive potential in APC-Truncated colon cancer cells. Nature Communications. 2018 Dec 1;9(1). 1106. https://doi.org/10.1038/s41467-018-03494-4