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

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

2041-4889
Zhou, Qing
f0e0fe00-80ef-46da-8be3-2dcc8f870f2c
Eldakhakhny, Sahar
4fc31720-4017-4d33-b124-951a756f90ba
Conforti, Franco
28bf123c-e42a-4fb5-8b26-f79e1095c586
Crosbie, Emma J.
ee31bba5-659e-4165-a707-aaee00f040e0
Melino, Gerry
e66da1c0-b7e7-4299-ba3b-13de37efdef6
Sayan, Berna S.
8ed99a56-197c-484f-80c2-b020f70e79fb
Zhou, Qing
f0e0fe00-80ef-46da-8be3-2dcc8f870f2c
Eldakhakhny, Sahar
4fc31720-4017-4d33-b124-951a756f90ba
Conforti, Franco
28bf123c-e42a-4fb5-8b26-f79e1095c586
Crosbie, Emma J.
ee31bba5-659e-4165-a707-aaee00f040e0
Melino, Gerry
e66da1c0-b7e7-4299-ba3b-13de37efdef6
Sayan, Berna S.
8ed99a56-197c-484f-80c2-b020f70e79fb

Zhou, Qing, Eldakhakhny, Sahar, Conforti, Franco, Crosbie, Emma J., Melino, Gerry and Sayan, Berna S. (2018) Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation article. Cell Death and Disease, 9 (5). (doi:10.1038/s41419-018-0521-1).

Record type: Article

Abstract

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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s41419-018-0521-1 - Version of Record
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Accepted/In Press date: 23 March 2018
e-pub ahead of print date: 2 May 2018
Published date: 2 May 2018

Identifiers

Local EPrints ID: 421170
URI: https://eprints.soton.ac.uk/id/eprint/421170
ISSN: 2041-4889
PURE UUID: 734bd5f7-629b-4019-ae2c-109d8c439f48

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Date deposited: 24 May 2018 16:30
Last modified: 13 Mar 2019 18:27

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