Polo-like kinase 1 facilitates loss of Pten tumor suppressorinduced prostate cancer formation

X. Shawn Liu, Bing Song, Bennett D. Elzey, Timothy L. Ratliff, Stephen F. Konieczny, Liang Cheng, Nihal Ahmad, Xiaoqi Liu

Research output: Contribution to journalArticle

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Abstract

Loss of the tumor suppressor Pten (phosphatase and tensin homolog deleted on chromosome 10) is thought to mediate the majority of prostate cancers, but the molecular mechanism remains elusive. In this study, we demonstrate that Pten-depleted cells suffer from mitotic stress and that nuclear function of Pten, but not its phosphatase activity, is required to reverse this stress phenotype. Further, depletion of Pten results in elevated expression of Polo-like kinase 1 (Plk1), a critical regulator of the cell cycle.Weshow that overexpression of Plk1 correlates with genetic inactivation of Pten during prostate neoplasia formation. Significantly, we find that elevated Plk1 is critical for Pten-depleted cells to adapt to mitotic stress for survival and that reintroduction of wild-type Pten into Pten-null prostate cancer cells reduces the survival dependence on Plk1. We further show that Plk1 confers the tumorigenic competence of Pten-deleted prostate cancer cells in a mouse xenograft model. These findings identify a role of Plk1 in facilitating loss of Pteninduced prostate cancer formation, which suggests that Plk1 might be a promising target for prostate cancer patients with inactivating Pten mutations.

Original languageEnglish
Pages (from-to)35795-35800
Number of pages6
JournalJournal of Biological Chemistry
Volume286
Issue number41
DOIs
StatePublished - Oct 14 2011

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Tumors
Prostatic Neoplasms
Neoplasms
Cells
Phosphoric Monoester Hydrolases
Chromosomes, Human, Pair 10
Chromosomes
polo-like kinase 1
Heterografts
Mental Competency
Prostate
Cell Survival
Cell Cycle
Phenotype
Mutation
Survival

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Liu, X. S., Song, B., Elzey, B. D., Ratliff, T. L., Konieczny, S. F., Cheng, L., ... Liu, X. (2011). Polo-like kinase 1 facilitates loss of Pten tumor suppressorinduced prostate cancer formation. Journal of Biological Chemistry, 286(41), 35795-35800. https://doi.org/10.1074/jbc.C111.269050

Polo-like kinase 1 facilitates loss of Pten tumor suppressorinduced prostate cancer formation. / Liu, X. Shawn; Song, Bing; Elzey, Bennett D.; Ratliff, Timothy L.; Konieczny, Stephen F.; Cheng, Liang; Ahmad, Nihal; Liu, Xiaoqi.

In: Journal of Biological Chemistry, Vol. 286, No. 41, 14.10.2011, p. 35795-35800.

Research output: Contribution to journalArticle

Liu, XS, Song, B, Elzey, BD, Ratliff, TL, Konieczny, SF, Cheng, L, Ahmad, N & Liu, X 2011, 'Polo-like kinase 1 facilitates loss of Pten tumor suppressorinduced prostate cancer formation', Journal of Biological Chemistry, vol. 286, no. 41, pp. 35795-35800. https://doi.org/10.1074/jbc.C111.269050
Liu, X. Shawn ; Song, Bing ; Elzey, Bennett D. ; Ratliff, Timothy L. ; Konieczny, Stephen F. ; Cheng, Liang ; Ahmad, Nihal ; Liu, Xiaoqi. / Polo-like kinase 1 facilitates loss of Pten tumor suppressorinduced prostate cancer formation. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 41. pp. 35795-35800.
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