title: Polo-like kinase 1 facilitates loss of Pten tumor suppressor-induced prostate cancer formation.
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. We show 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 Pten-induced prostate cancer formation, which suggests that Plk1 might be a promising target for prostate cancer patients with inactivating Pten mutations.
authors: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907; Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors: X Shawn
authors: XS
authors: Liu
authors: Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907; Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.
authors: Bing
authors: B
authors: Song
authors: Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907; Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana 47907.
authors: Bennett D
authors: BD
authors: Elzey
authors: Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907; Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana 47907.
authors: Timothy L
authors: TL
authors: Ratliff
authors: Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907; Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.
authors: Stephen F
authors: SF
authors: Konieczny
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.
authors: Liang
authors: L
authors: Cheng
authors: Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706.
authors: Nihal
authors: N
authors: Ahmad
authors: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907; Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907. Electronic address: liu8@purdue.edu.
authors: Xiaoqi
authors: X
authors: Liu
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis; D009368:Neoplasm Transplantation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D014183:Transplantation, Heterologous; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D051059:PTEN Phosphohydrolase; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C494929:PTEN protein, human; C487757:Pten protein, mouse