Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/10734 |
| _version_ | 1811200213323350016 |
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| author | Jianguo Wu Andrei I Ivanov Paul B Fisher Zheng Fu |
| author_facet | Jianguo Wu Andrei I Ivanov Paul B Fisher Zheng Fu |
| author_sort | Jianguo Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:59:50Z |
| format | Article |
| id | doaj.art-04021b9f4eb44042be60ab919c21d034 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:59:50Z |
| publishDate | 2016-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-04021b9f4eb44042be60ab919c21d0342022-12-22T03:52:41ZengeLife Sciences Publications LtdeLife2050-084X2016-03-01510.7554/eLife.10734Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signalingJianguo Wu0Andrei I Ivanov1Paul B Fisher2Zheng Fu3https://orcid.org/0000-0003-0837-3728Department 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 StatesDepartment 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 StatesDepartment 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 StatesDepartment 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 StatesPolo-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.https://elifesciences.org/articles/10734polo-like kinase 1epithelial-to-mesenchymal transitioncell migrationCRAFprostate cancerinvasion |
| spellingShingle | Jianguo Wu Andrei I Ivanov Paul B Fisher Zheng Fu Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling eLife polo-like kinase 1 epithelial-to-mesenchymal transition cell migration CRAF prostate cancer invasion |
| title | Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling |
| title_full | Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling |
| title_fullStr | Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling |
| title_full_unstemmed | Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling |
| title_short | Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling |
| title_sort | polo like kinase 1 induces epithelial to mesenchymal transition and promotes epithelial cell motility by activating craf erk signaling |
| topic | polo-like kinase 1 epithelial-to-mesenchymal transition cell migration CRAF prostate cancer invasion |
| url | https://elifesciences.org/articles/10734 |
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