DOI: 10.1073/pnas.1031523100. Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells

Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells

10.1073/pnas.1031523100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Elevated expression of mammalian polo-like kinase (Plk)1 occurs in many different types of cancers, and Plk1 has been proposed as a novel diagnostic marker for several tumors. We used the recently developed vector-based small interfering RNA technique to specifically deplete Plk1 in cancer cells. We found that Plk1 depletion dramatically inhibited cell proliferation, decreased viability, and resulted in cell-cycle arrest with 4 N DNA content. The formation of dumbbell-like chromatin structure suggests the inability of these cells to completely separate the sister chromatids at the onset of anaphase. Plk1 depletion induced apoptosis, as indicated by the appearance of subgenomic DNA in fluorescence-activated cell-sorter (FACS) profiles, the activation of caspase 3, and the formation of fragmented nuclei. Plk1-depletion-induced apoptosis was partially reversed by cotransfection of nondegradable mouse Plk1 constructs. In addition, the p53 pathway was shown to be involved in Plk1-depletion-induced apoptosis. DNA damage occurred in Plk1-depleted cells and inhibition of ATM strongly potentiated the lethality of Plk1 depletion. Although p53 is stabilized in Plk1-depleted cells, DNA damage also occurs in p53 −/− cells. These data support the notion that disruption of Plk1 function could be an important application in cancer therapy.

Bibliography

Liu, X., & Erikson, R. L. (2003). Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells. Proceedings of the National Academy of Sciences, 100(10), 5789â5794.

Authors 2

Xiaoqi Liu (first)
Raymond L. Erikson (additional)

References 19 Referenced 400

10.1101/gad.12.24.3777
10.1016/S0955-0674(98)80121-X
10.1073/pnas.132269599
K Strebhardt PLK (Polo-Like Kinase): Encyclopedia of Molecular Medicine, ed T E Creighton (Wiley, New York), pp. 2530–2532 (2001). / PLK (Polo-Like Kinase): Encyclopedia of Molecular Medicine by Strebhardt K (2001)
R Knecht, R Elez, M Oechler, C Solbach, C von Ilberg, K Strebhardt Cancer Res 59, 2794–2797 (1999). / Cancer Res by Knecht R (1999)
10.1002/1097-0215(20001120)89:6<535::AID-IJC12>3.0.CO;2-E
10.1006/bbrc.1997.6633
10.1073/pnas.082117599
10.1038/nrc776
10.1016/0092-8674(95)90513-8
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10.1016/S0960-9822(00)00610-2
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J N Sarkaria, E C Busby, R S Tibbetts, P Roos, Y Taya, L M Karnitz, R T Abraham Cancer Res 59, 4375–4382 (1999). / Cancer Res by Sarkaria J N (1999)
J N Sarkaria, R S Tibbetts, E C Busby, A P Kennedy, D E Hill, R T Abraham Cancer Res 58, 4375–4382 (1998). / Cancer Res by Sarkaria J N (1998)
10.1016/S0092-8674(01)00362-2
10.1074/jbc.273.10.5858
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10.1093/jnci/94.24.1863

Dates

Type	When
Created	22 years, 3 months ago (May 13, 2003, 2:28 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 7:36 p.m.)
Indexed	1 month ago (July 28, 2025, 5:47 p.m.)
Issued	22 years, 3 months ago (May 5, 2003)
Published	22 years, 3 months ago (May 5, 2003)
Published Online	22 years, 3 months ago (May 5, 2003)
Published Print	22 years, 3 months ago (May 13, 2003)

Funders 0

None

BibTeX

@article{Liu_2003, title={Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1031523100}, DOI={10.1073/pnas.1031523100}, number={10}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Liu, Xiaoqi and Erikson, Raymond L.}, year={2003}, month=may, pages={5789–5794} }

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