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

• Published in: Cell death & disease 2018-05, Vol.9 (5), p.504-10, Article 504
• Main Authors: Zhou, Qing, Eldakhakhny, Sahar, Conforti, Franco, Crosbie, Emma J., Melino, Gerry, Sayan, Berna S.
• Format: Article
• Language: English
• Subjects: 13/89; 38/109; 38/90; 42/70; 82/29; 82/80; 96/1; 96/106; 96/98; Antibodies; Biochemistry; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Cancer; Cell Biology; Cell Culture; Cell growth; Cell Line, Tumor; Cell Proliferation; Decision making; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endometrium; Endometrium - metabolism; Endometrium - pathology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors; Glycogen Synthase Kinase 3 beta - genetics; Glycogen Synthase Kinase 3 beta - metabolism; Hormone replacement therapy; Humans; Immunology; Life Sciences; Lithium Chloride - pharmacology; Phosphorylation; Prognosis; Protein Kinase Inhibitors - pharmacology; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; Transcription; Tumor cell lines; Tumors; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - antagonists & inhibitors; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-0521-1

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.