title: Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling.
abstract: Polo-like kinase 1 (PLK1) is a key cell cycle regulator implicated in the development of various cancers, including prostate cancer. However, the functions of PLK1 beyond cell cycle regulation remain poorly characterized. Here, we report that PLK1 overexpression in prostate epithelial cells triggers oncogenic transformation. It also results in dramatic transcriptional reprogramming of the cells, leading to epithelial-to-mesenchymal transition (EMT) and stimulation of cell migration and invasion. Consistently, PLK1 downregulation in metastatic prostate cancer cells enhances epithelial characteristics and inhibits cell motility. The signaling mechanisms underlying the observed cellular effects of PLK1 involve direct PLK1-dependent phosphorylation of CRAF with subsequent stimulation of the MEK1/2-ERK1/2-Fra1-ZEB1/2 signaling pathway. Our findings highlight novel non-canonical functions of PLK1 as a key regulator of EMT and cell motility in normal prostate epithelium and prostate cancer. This study also uncovers a previously unanticipated role of PLK1 as a potent activator of MAPK signaling.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, United States.|VCU Institute of Molecular Medicine, Virginia Commonwealth University School of Medicine, Richmond, United States.|VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, United States.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, United States.|VCU Institute of Molecular Medicine, Virginia Commonwealth University School of Medicine, Richmond, United States.|VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, United States.
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Ivanov
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, United States.|VCU Institute of Molecular Medicine, Virginia Commonwealth University School of Medicine, Richmond, United States.|VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, United States.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, United States.|VCU Institute of Molecular Medicine, Virginia Commonwealth University School of Medicine, Richmond, United States.|VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, United States.
authors.forename: Zheng
authors.identifier: http://orcid.org/0000-0003-0837-3728
authors.initials: Z
authors.lastname: Fu
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D048008:TNF Receptor-Associated Factor 3; D000097869:Polo-Like Kinase 1
keywords: CRAF; cell biology; cell migration; epithelial-to-mesenchymal transition; human; human biology; invasion; medicine; mouse; polo-like kinase 1; prostate cancer