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

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journal contribution
posted on 11.10.2018, 14:48 by Qing Zhou, Sahar Eldakhakhny, Franco Conforti, Emma J. Crosbie, Gerry Melino, Berna S. Sayan
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.

Funding

This work was supported by the funds given to B.S.S. by the UoM. E.J.C. is supported by an NIHR Clinician Scientist fellowship (NIHR-CS-012-009).

History

Citation

Cell Death & Disease, 2018, 9, 504

Version

VoR (Version of Record)

Published in

Cell Death & Disease

Publisher

Springer Nature for Associazione Differenziamento e Morte Cellulare

eissn

2041-4889

Acceptance date

23/03/2018

Copyright date

2018

Available date

11/10/2018

Publisher version

https://www.nature.com/articles/s41419-018-0521-1

Notes

Supplementary Information accompanies this paper at https://doi.org/10.1038/s41419-018-0521-1

Language

en

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