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Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation

Endometrial cancer is one of the most common gynaecological cancers in developed countries. Its incidence has increased 20% over the last decade and the death rate has increased >100% over the past two decades. Current models for prediction of prognosis and treatment response are suboptimal, and...

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Autores principales: Zhou, Qing, Eldakhakhny, Sahar, Conforti, Franco, Crosbie, Emma J., Melino, Gerry, Sayan, Berna S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938710/
https://www.ncbi.nlm.nih.gov/pubmed/29724995
http://dx.doi.org/10.1038/s41419-018-0521-1
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author Zhou, Qing
Eldakhakhny, Sahar
Conforti, Franco
Crosbie, Emma J.
Melino, Gerry
Sayan, Berna S.
author_facet Zhou, Qing
Eldakhakhny, Sahar
Conforti, Franco
Crosbie, Emma J.
Melino, Gerry
Sayan, Berna S.
author_sort Zhou, Qing
collection PubMed
description Endometrial cancer is one of the most common gynaecological cancers in developed countries. Its incidence has increased 20% over the last decade and the death rate has increased >100% over the past two decades. Current models for prediction of prognosis and treatment response are suboptimal, and as such biomarkers to support clinical decision-making and contribute to individualised treatment are needed. In this study, we show that the E3-ubiquitin ligase PIR2/RNF144B is a potential targetable biomarker in endometrial cancer. At transcript level, it is expressed both in normal endometrium and tumour samples, but at protein level, it is expressed in tumours only. By using endometrial cancer cell lines, we demonstrated that PIR2/RNF144B is stabilised via phosphorylation downstream of GSK3β and this is necessary for the proliferation of endometrial cancer cells, in the absence of oestrogenic growth stimuli. Here, inactivation of GSK3β activity is associated with loss of PIR2/RNF144B protein and consequent inhibition of cell proliferation. Our results, therefore, substantiate PIR2/RNF144B as a novel candidate for targeted therapy in endometrial cancer.
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spelling pubmed-59387102018-05-09 Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation Zhou, Qing Eldakhakhny, Sahar Conforti, Franco Crosbie, Emma J. Melino, Gerry Sayan, Berna S. Cell Death Dis Article Endometrial cancer is one of the most common gynaecological cancers in developed countries. Its incidence has increased 20% over the last decade and the death rate has increased >100% over the past two decades. Current models for prediction of prognosis and treatment response are suboptimal, and as such biomarkers to support clinical decision-making and contribute to individualised treatment are needed. In this study, we show that the E3-ubiquitin ligase PIR2/RNF144B is a potential targetable biomarker in endometrial cancer. At transcript level, it is expressed both in normal endometrium and tumour samples, but at protein level, it is expressed in tumours only. By using endometrial cancer cell lines, we demonstrated that PIR2/RNF144B is stabilised via phosphorylation downstream of GSK3β and this is necessary for the proliferation of endometrial cancer cells, in the absence of oestrogenic growth stimuli. Here, inactivation of GSK3β activity is associated with loss of PIR2/RNF144B protein and consequent inhibition of cell proliferation. Our results, therefore, substantiate PIR2/RNF144B as a novel candidate for targeted therapy in endometrial cancer. Nature Publishing Group UK 2018-05-02 /pmc/articles/PMC5938710/ /pubmed/29724995 http://dx.doi.org/10.1038/s41419-018-0521-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhou, Qing
Eldakhakhny, Sahar
Conforti, Franco
Crosbie, Emma J.
Melino, Gerry
Sayan, Berna S.
Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation
title Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation
title_full Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation
title_fullStr Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation
title_full_unstemmed Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation
title_short Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation
title_sort pir2/rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938710/
https://www.ncbi.nlm.nih.gov/pubmed/29724995
http://dx.doi.org/10.1038/s41419-018-0521-1
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