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Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling
Plk2 is a target of p53. Our previous studies demonstrated that with wild-type p53, Plk2 impacts mTOR signaling in the same manner as TSC1, and Plk2-deficient tumors grew larger than control. Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. We in...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849802/ https://www.ncbi.nlm.nih.gov/pubmed/29448085 http://dx.doi.org/10.1016/j.neo.2018.01.004 |
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author | Matthew, Elizabeth M. Yang, Zhaohai Peri, Suraj Andrake, Mark Dunbrack, Roland Ross, Eric El-Deiry, Wafik S. |
author_facet | Matthew, Elizabeth M. Yang, Zhaohai Peri, Suraj Andrake, Mark Dunbrack, Roland Ross, Eric El-Deiry, Wafik S. |
author_sort | Matthew, Elizabeth M. |
collection | PubMed |
description | Plk2 is a target of p53. Our previous studies demonstrated that with wild-type p53, Plk2 impacts mTOR signaling in the same manner as TSC1, and Plk2-deficient tumors grew larger than control. Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. We investigated Plk2’s tumor suppressor functions in relationship to mTOR signaling. Archival specimens from 12 colorectal adenocarcinomas were stained for markers including Plk2, phosphorylated mTOR (serine 2448) and ribosomal S6 (Serine 235/236). We show that Plk2 is expressed in normal colon, with a punctate staining pattern in supranuclear cytoplasm. In colorectal adenocarcinoma, Plk2 demonstrates complete or partial loss of expression. Strong expression of phosphorylated mTOR is observed in the invasive front. Phosphorylated S6 expression partially correlates with phosphorylated mTOR expression but appears more diffuse in some cases. p53 and Ki67 expression is diffuse, in the subset of cases examined. In order to determine whether Plk2 is lost prior to the development of invasive cancer, 8 colon polyps from 6 patients were evaluated for Plk2 expression. All polyps are positive for Plk2. A Cancer Genome Atlas search identified Plk2 mutations to be infrequent in colorectal adenocarcinomas. Neither Plk2 methylation (in the gene body) nor copy number variations correlated with changes in mRNA expression levels. Loss of Plk2 expression along with accentuated expression of phosphorylated mTOR and phosphorylated S6 at the invasive front in some colorectal carcinomas is consistent with previous findings that an interaction between Plk2 and TSC1 / mTOR signaling molecules plays a role in tumor suppression. Plk2 protein expression is lost at the same stage in colorectal carcinogenesis as p53. The p53 dependence of Plk2 loss and tumor suppressor function in relationship to mTOR signaling may have therapeutic implications. |
format | Online Article Text |
id | pubmed-5849802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58498022018-03-16 Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling Matthew, Elizabeth M. Yang, Zhaohai Peri, Suraj Andrake, Mark Dunbrack, Roland Ross, Eric El-Deiry, Wafik S. Neoplasia Original article Plk2 is a target of p53. Our previous studies demonstrated that with wild-type p53, Plk2 impacts mTOR signaling in the same manner as TSC1, and Plk2-deficient tumors grew larger than control. Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. We investigated Plk2’s tumor suppressor functions in relationship to mTOR signaling. Archival specimens from 12 colorectal adenocarcinomas were stained for markers including Plk2, phosphorylated mTOR (serine 2448) and ribosomal S6 (Serine 235/236). We show that Plk2 is expressed in normal colon, with a punctate staining pattern in supranuclear cytoplasm. In colorectal adenocarcinoma, Plk2 demonstrates complete or partial loss of expression. Strong expression of phosphorylated mTOR is observed in the invasive front. Phosphorylated S6 expression partially correlates with phosphorylated mTOR expression but appears more diffuse in some cases. p53 and Ki67 expression is diffuse, in the subset of cases examined. In order to determine whether Plk2 is lost prior to the development of invasive cancer, 8 colon polyps from 6 patients were evaluated for Plk2 expression. All polyps are positive for Plk2. A Cancer Genome Atlas search identified Plk2 mutations to be infrequent in colorectal adenocarcinomas. Neither Plk2 methylation (in the gene body) nor copy number variations correlated with changes in mRNA expression levels. Loss of Plk2 expression along with accentuated expression of phosphorylated mTOR and phosphorylated S6 at the invasive front in some colorectal carcinomas is consistent with previous findings that an interaction between Plk2 and TSC1 / mTOR signaling molecules plays a role in tumor suppression. Plk2 protein expression is lost at the same stage in colorectal carcinogenesis as p53. The p53 dependence of Plk2 loss and tumor suppressor function in relationship to mTOR signaling may have therapeutic implications. Neoplasia Press 2018-02-12 /pmc/articles/PMC5849802/ /pubmed/29448085 http://dx.doi.org/10.1016/j.neo.2018.01.004 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Matthew, Elizabeth M. Yang, Zhaohai Peri, Suraj Andrake, Mark Dunbrack, Roland Ross, Eric El-Deiry, Wafik S. Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling |
title | Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling |
title_full | Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling |
title_fullStr | Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling |
title_full_unstemmed | Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling |
title_short | Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling |
title_sort | plk2 loss commonly occurs in colorectal carcinomas but not adenomas: relationship to mtor signaling |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849802/ https://www.ncbi.nlm.nih.gov/pubmed/29448085 http://dx.doi.org/10.1016/j.neo.2018.01.004 |
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