title: The role of polo-like kinase 1 in carcinogenesis: cause or consequence?
abstract: Polo-like kinase 1 (Plk1) is a well-established mitotic regulator with a diverse range of biologic functions continually being identified throughout the cell cycle. Preclinical evidence suggests that the molecular targeting of Plk1 could be an effective therapeutic strategy in a wide range of cancers; however, that success has yet to be translated to the clinical level. The lack of clinical success has raised the question of whether there is a true oncogenic addiction to Plk1 or if its overexpression in tumors is solely an artifact of increased cellular proliferation. In this review, we address the role of Plk1 in carcinogenesis by discussing the cell cycle and DNA damage response with respect to their associations with classic oncogenic and tumor suppressor pathways that contribute to the transcriptional regulation of Plk1. A thorough examination of the available literature suggests that Plk1 activity can be dysregulated through key transformative pathways, including both p53 and pRb. On the basis of the available literature, it may be somewhat premature to draw a definitive conclusion on the role of Plk1 in carcinogenesis. However, evidence supports the notion that oncogene dependence on Plk1 is not a late occurrence in carcinogenesis and it is likely that Plk1 plays an active role in carcinogenic transformation.
authors.affiliation: Authors' Affiliations: Department of Dermatology; Molecular and Environmental Toxicology Center, University of Wisconsin; William S. Middleton Memorial VA Hospital, Madison, Wisconsin; and Department of Biochemistry, Purdue University, West Lafayette, Indiana.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Cholewa
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
authors.forename: Nihal
authors.initials: N
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000502:physiology*; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D008938:Mitosis / Q000235:genetics; D009857:Oncogenes / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1