USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment.
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.
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Rachel Isaksson
RI
Vogel
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Tanya
T
Pulver
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.|Department of Women's Health, University Hospital Tuebingen University, Tuebingen, Germany.
Wiebke
W
Heilmann
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Ashley
A
Mooneyham
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Sally
S
Mullany
Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Xianda
X
Zhao
Department of Pathology and Laboratory Medicine, University of Minnesota, Minneapolis, MN, USA.
Maryam
M
Shahi
Department of Pathology and Laboratory Medicine, University of Minnesota, Minneapolis, MN, USA.
James
J
Richter
Department of Pathology and Laboratory Medicine, University of Minnesota, Minneapolis, MN, USA.
Molly
M
Klein
Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN, USA.
Liqiang
L
Chen
Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN, USA.
Rui
R
Ding
Gynecologic Oncology, Hematology & Oncology Department, UCLA Medical Center, Santa Monica, CA, USA.
Gottfried
G
Konecny
Department of Women's Health, University Hospital Tuebingen University, Tuebingen, Germany.
Stefan
S
Kommoss
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Boris
B
Winterhoff
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Rahel
R
Ghebre
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Martina
M
Bazzaro
D000368:Aged; D001381:Azepines / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000097:blood*; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000201:enzymology / Q000473:pathology; D011379:Prognosis; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood*
D001381:Azepines; D001597:Benzylidene Compounds; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; C509299:USP14 protein, human; C000623193:VLX1570; D016190:Carboplatin; D043222:Ubiquitin Thiolesterase
USP14; VLX1570; biomarker; endometrial cancer; recurrence