The CINs of Polo-Like Kinase 1 in Cancer
Polo-like kinase 1 (PLK1) is overexpressed near ubiquitously across all cancer types and dysregulation of this enzyme is closely tied to increased chromosomal instability and tumor heterogeneity. PLK1 is a mitotic kinase with a critical role in maintaining chromosomal integrity through its function...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/10/2953 |
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| author | Chelsea E. Cunningham Mackenzie J. MacAuley Frederick S. Vizeacoumar Omar Abuhussein Andrew Freywald Franco J. Vizeacoumar |
| author_facet | Chelsea E. Cunningham Mackenzie J. MacAuley Frederick S. Vizeacoumar Omar Abuhussein Andrew Freywald Franco J. Vizeacoumar |
| author_sort | Chelsea E. Cunningham |
| collection | DOAJ |
| description | Polo-like kinase 1 (PLK1) is overexpressed near ubiquitously across all cancer types and dysregulation of this enzyme is closely tied to increased chromosomal instability and tumor heterogeneity. PLK1 is a mitotic kinase with a critical role in maintaining chromosomal integrity through its function in processes ranging from the mitotic checkpoint, centrosome biogenesis, bipolar spindle formation, chromosome segregation, DNA replication licensing, DNA damage repair, and cytokinesis. The relation between dysregulated PLK1 and chromosomal instability (CIN) makes it an attractive target for cancer therapy. However, clinical trials with PLK1 inhibitors as cancer drugs have generally displayed poor responses or adverse side-effects. This is in part because targeting CIN regulators, including PLK1, can elevate CIN to lethal levels in normal cells, affecting normal physiology. Nevertheless, aiming at related genetic interactions, such as synthetic dosage lethal (SDL) interactions of PLK1 instead of PLK1 itself, can help to avoid the detrimental side effects associated with increased levels of CIN. Since PLK1 overexpression contributes to tumor heterogeneity, targeting SDL interactions may also provide an effective strategy to suppressing this malignant phenotype in a personalized fashion. |
| first_indexed | 2024-03-10T15:40:20Z |
| format | Article |
| id | doaj.art-488446f8a7084291ac1f62a1c079b6fc |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:40:20Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-488446f8a7084291ac1f62a1c079b6fc2023-11-20T16:50:18ZengMDPI AGCancers2072-66942020-10-011210295310.3390/cancers12102953The CINs of Polo-Like Kinase 1 in CancerChelsea E. Cunningham0Mackenzie J. MacAuley1Frederick S. Vizeacoumar2Omar Abuhussein3Andrew Freywald4Franco J. Vizeacoumar5Department of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaDepartment of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaDepartment of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaCollege of Pharmacy, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK S7N 2Z4, CanadaDepartment of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaDepartment of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaPolo-like kinase 1 (PLK1) is overexpressed near ubiquitously across all cancer types and dysregulation of this enzyme is closely tied to increased chromosomal instability and tumor heterogeneity. PLK1 is a mitotic kinase with a critical role in maintaining chromosomal integrity through its function in processes ranging from the mitotic checkpoint, centrosome biogenesis, bipolar spindle formation, chromosome segregation, DNA replication licensing, DNA damage repair, and cytokinesis. The relation between dysregulated PLK1 and chromosomal instability (CIN) makes it an attractive target for cancer therapy. However, clinical trials with PLK1 inhibitors as cancer drugs have generally displayed poor responses or adverse side-effects. This is in part because targeting CIN regulators, including PLK1, can elevate CIN to lethal levels in normal cells, affecting normal physiology. Nevertheless, aiming at related genetic interactions, such as synthetic dosage lethal (SDL) interactions of PLK1 instead of PLK1 itself, can help to avoid the detrimental side effects associated with increased levels of CIN. Since PLK1 overexpression contributes to tumor heterogeneity, targeting SDL interactions may also provide an effective strategy to suppressing this malignant phenotype in a personalized fashion.https://www.mdpi.com/2072-6694/12/10/2953Polo-like kinase 1chromosomal instabilityDNA damage repairsynthetic dosage lethality |
| spellingShingle | Chelsea E. Cunningham Mackenzie J. MacAuley Frederick S. Vizeacoumar Omar Abuhussein Andrew Freywald Franco J. Vizeacoumar The CINs of Polo-Like Kinase 1 in Cancer Cancers Polo-like kinase 1 chromosomal instability DNA damage repair synthetic dosage lethality |
| title | The CINs of Polo-Like Kinase 1 in Cancer |
| title_full | The CINs of Polo-Like Kinase 1 in Cancer |
| title_fullStr | The CINs of Polo-Like Kinase 1 in Cancer |
| title_full_unstemmed | The CINs of Polo-Like Kinase 1 in Cancer |
| title_short | The CINs of Polo-Like Kinase 1 in Cancer |
| title_sort | cins of polo like kinase 1 in cancer |
| topic | Polo-like kinase 1 chromosomal instability DNA damage repair synthetic dosage lethality |
| url | https://www.mdpi.com/2072-6694/12/10/2953 |
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