Cargando…
Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma
Centrosomes duplicate only once in coordination with the DNA replication cycle and have an important role in segregating genetic material. In contrast, most cancer cells have centrosome aberrations, including supernumerary centrosomes, and this correlates with aneuploidy and genetic instability. The...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435684/ https://www.ncbi.nlm.nih.gov/pubmed/32067956 http://dx.doi.org/10.1016/j.jid.2020.01.024 |
_version_ | 1783572379460435968 |
---|---|
author | Patel, Shyamal Wilkinson, Christopher J. Sviderskaya, Elena V. |
author_facet | Patel, Shyamal Wilkinson, Christopher J. Sviderskaya, Elena V. |
author_sort | Patel, Shyamal |
collection | PubMed |
description | Centrosomes duplicate only once in coordination with the DNA replication cycle and have an important role in segregating genetic material. In contrast, most cancer cells have centrosome aberrations, including supernumerary centrosomes, and this correlates with aneuploidy and genetic instability. The tumor suppressors p16 (CDKN2A) and p15 (CDKN2B) (encoded by the familial melanoma CDKN2 locus) inhibit CDK4/6 activity and have important roles in cellular senescence. p16 is also associated with suppressing centrosomal aberrations in breast cancer; however, the role of p15 in centrosome amplification is unknown. Here, we investigated the relationship between p15 and p16 expression, centrosome number abnormalities, and melanoma progression in cell lines derived from various stages of melanoma progression. We found that normal human melanocyte lines did not exhibit centrosome number abnormalities, whereas those from later stages of melanoma did. Additionally, under conditions of S-phase block, p15 and p16 status determined whether centrosome overduplication would occur. Indeed, removal of p15 from p16-negative cell lines derived from various stages of melanoma progression changed cells that previously would not overduplicate their centrosomes into cells that did. Although this study used cell lines in vitro, it suggests that, during clinical melanoma progression, sequential loss of p15 and p16 provides conditions for centrosome duplication to become deregulated with consequences for genome instability. |
format | Online Article Text |
id | pubmed-7435684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-74356842020-09-01 Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma Patel, Shyamal Wilkinson, Christopher J. Sviderskaya, Elena V. J Invest Dermatol Article Centrosomes duplicate only once in coordination with the DNA replication cycle and have an important role in segregating genetic material. In contrast, most cancer cells have centrosome aberrations, including supernumerary centrosomes, and this correlates with aneuploidy and genetic instability. The tumor suppressors p16 (CDKN2A) and p15 (CDKN2B) (encoded by the familial melanoma CDKN2 locus) inhibit CDK4/6 activity and have important roles in cellular senescence. p16 is also associated with suppressing centrosomal aberrations in breast cancer; however, the role of p15 in centrosome amplification is unknown. Here, we investigated the relationship between p15 and p16 expression, centrosome number abnormalities, and melanoma progression in cell lines derived from various stages of melanoma progression. We found that normal human melanocyte lines did not exhibit centrosome number abnormalities, whereas those from later stages of melanoma did. Additionally, under conditions of S-phase block, p15 and p16 status determined whether centrosome overduplication would occur. Indeed, removal of p15 from p16-negative cell lines derived from various stages of melanoma progression changed cells that previously would not overduplicate their centrosomes into cells that did. Although this study used cell lines in vitro, it suggests that, during clinical melanoma progression, sequential loss of p15 and p16 provides conditions for centrosome duplication to become deregulated with consequences for genome instability. Elsevier 2020-09 /pmc/articles/PMC7435684/ /pubmed/32067956 http://dx.doi.org/10.1016/j.jid.2020.01.024 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Patel, Shyamal Wilkinson, Christopher J. Sviderskaya, Elena V. Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma |
title | Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma |
title_full | Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma |
title_fullStr | Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma |
title_full_unstemmed | Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma |
title_short | Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma |
title_sort | loss of both cdkn2a and cdkn2b allows for centrosome overduplication in melanoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435684/ https://www.ncbi.nlm.nih.gov/pubmed/32067956 http://dx.doi.org/10.1016/j.jid.2020.01.024 |
work_keys_str_mv | AT patelshyamal lossofbothcdkn2aandcdkn2ballowsforcentrosomeoverduplicationinmelanoma AT wilkinsonchristopherj lossofbothcdkn2aandcdkn2ballowsforcentrosomeoverduplicationinmelanoma AT sviderskayaelenav lossofbothcdkn2aandcdkn2ballowsforcentrosomeoverduplicationinmelanoma |