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Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis
Forty years of research has proven beyond any doubt that p53 is a key regulator of many aspects of cellular physiology. It is best known for its tumor suppressor function, but it is also a regulator of processes important for maintenance of homeostasis and stress response. Its activity is generally...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072881/ https://www.ncbi.nlm.nih.gov/pubmed/32079237 http://dx.doi.org/10.3390/ijms21041334 |
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author | Roszkowska, Katarzyna A. Gizinski, Slawomir Sady, Maria Gajewski, Zdzislaw Olszewski, Maciej B. |
author_facet | Roszkowska, Katarzyna A. Gizinski, Slawomir Sady, Maria Gajewski, Zdzislaw Olszewski, Maciej B. |
author_sort | Roszkowska, Katarzyna A. |
collection | PubMed |
description | Forty years of research has proven beyond any doubt that p53 is a key regulator of many aspects of cellular physiology. It is best known for its tumor suppressor function, but it is also a regulator of processes important for maintenance of homeostasis and stress response. Its activity is generally antiproliferative and when the cell is damaged beyond repair or intensely stressed the p53 protein contributes to apoptosis. Given its key role in preventing cancer it is no wonder that it is the most frequently mutated gene in human cancer. Surprisingly, a subset of missense mutations occurring in p53 (gain-of-function) cause it to lose its suppressor activity and acquire new functionalities that turn the tumor suppressor protein into an oncoprotein. A solid body of evidence exists demonstrating increased malignancy of cancers with mutated p53 in all aspects considered “hallmarks of cancer”. In this review, we summarize current findings concerning the cellular processes altered by gain-of-function mutations in p53 and their influence on cancer invasiveness and metastasis. We also present the variety of molecular mechanisms regulating these processes, including microRNA, direct transcriptional regulation, protein–protein interactions, and more. |
format | Online Article Text |
id | pubmed-7072881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70728812020-03-19 Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis Roszkowska, Katarzyna A. Gizinski, Slawomir Sady, Maria Gajewski, Zdzislaw Olszewski, Maciej B. Int J Mol Sci Review Forty years of research has proven beyond any doubt that p53 is a key regulator of many aspects of cellular physiology. It is best known for its tumor suppressor function, but it is also a regulator of processes important for maintenance of homeostasis and stress response. Its activity is generally antiproliferative and when the cell is damaged beyond repair or intensely stressed the p53 protein contributes to apoptosis. Given its key role in preventing cancer it is no wonder that it is the most frequently mutated gene in human cancer. Surprisingly, a subset of missense mutations occurring in p53 (gain-of-function) cause it to lose its suppressor activity and acquire new functionalities that turn the tumor suppressor protein into an oncoprotein. A solid body of evidence exists demonstrating increased malignancy of cancers with mutated p53 in all aspects considered “hallmarks of cancer”. In this review, we summarize current findings concerning the cellular processes altered by gain-of-function mutations in p53 and their influence on cancer invasiveness and metastasis. We also present the variety of molecular mechanisms regulating these processes, including microRNA, direct transcriptional regulation, protein–protein interactions, and more. MDPI 2020-02-17 /pmc/articles/PMC7072881/ /pubmed/32079237 http://dx.doi.org/10.3390/ijms21041334 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Roszkowska, Katarzyna A. Gizinski, Slawomir Sady, Maria Gajewski, Zdzislaw Olszewski, Maciej B. Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis |
title | Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis |
title_full | Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis |
title_fullStr | Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis |
title_full_unstemmed | Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis |
title_short | Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis |
title_sort | gain-of-function mutations in p53 in cancer invasiveness and metastasis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072881/ https://www.ncbi.nlm.nih.gov/pubmed/32079237 http://dx.doi.org/10.3390/ijms21041334 |
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