USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment
Autor: | Liqiang Chen, Gottfried E. Konecny, Sally A. Mullany, Molly Klein, Rui Ding, Rahel G Ghebre, Stefan Kommoss, J. Richter, Ashley Mooneyham, Rachel Isaksson Vogel, Maryam Shahi, Martina Bazzaro, W Heilmann, Boris Winterhoff, Tanya Pulver, Xianda Zhao |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty recurrence Cell cycle checkpoint Cell Survival medicine.medical_treatment Disease Protein degradation Benzylidene Compounds Carboplatin Targeted therapy 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Biomarkers Tumor medicine Humans Molecular Targeted Therapy Enzyme Inhibitors Aged Cell Proliferation Cell growth business.industry Endometrial cancer Cancer Azepines Middle Aged Prognosis medicine.disease USP14 Endometrial Neoplasms 3. Good health 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis endometrial cancer Cancer research biomarker Biomarker (medicine) Female Neoplasm Recurrence Local business Ubiquitin Thiolesterase Research Paper VLX1570 |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
DOI: | 10.18632/oncotarget.8821 |
Popis: | Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. Most endometrial cancer cases are diagnosed at an early stage and have good prognosis. Unfortunately a subset of patients with early stage and low grade disease experience recurrence for reasons that remain unclear. Recurrence is often accompanied by chemoresistance and high mortality. Deubiquitinating enzymes (DUBs) are key components of the ubiquitin-dependent protein degradation pathway and act as master regulators in a number of metabolic processes including cell growth, differentiation, and apoptosis. DUBs have been shown to be upregulated in a number of human cancers and their aberrant activity has been linked to cancer progression, initiation and onset of chemoresistance. Thus, selective inhibition of DUBs has been proposed as a targeted therapy for cancer treatment. This study suggests the DUB USP14 as a promising biomarker for stratifying endometrial cancer patients at diagnosis based on their risk of recurrence. Further USP14 is expressed along with the marker of proliferation Ki67 in endometrial cancer cells in situ. Lastly, pharmacological targeting of USP14 with the FDA approved small-molecule inhibitor VLX1570, decreases cell viability in chemotherapy resistant endometrial cancer cells with a mechanism consistent with cell cycle arrest and caspase-3 mediated apoptosis. |
Databáze: | OpenAIRE |
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