Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Nuclear receptor NR5A2 negatively regulates cell proliferation and tumor growth in nervous system malignancies
Δημιουργός/Συγγραφέας:	Gkikas, Dimitrios [EL] Στέλλας, Δημήτρης[EN] Stellas, Dimitris Polissidis, Alexia Manolakou, Theodora Kokotou, Maroula G Kokotos, George Politis, Panagiotis K
Εκδότης:	National Academy of Sciences
Ημερομηνία:	2021-09-28
Γλώσσα:	Αγγλικά
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.2015243118
Άλλο:	34561301
Περίληψη:	Nervous system malignancies are characterized by rapid progression and poor survival rates. These clinical observations underscore the need for novel therapeutic insights and pharmacological targets. To this end, here, we identify the orphan nuclear receptor NR5A2/LRH1 as a negative regulator of cancer cell proliferation and promising pharmacological target for nervous system-related tumors. In particular, clinical data from publicly available databases suggest that high expression levels of NR5A2 are associated with favorable prognosis in patients with glioblastoma and neuroblastoma tumors. Consistently, we experimentally show that NR5A2 is sufficient to strongly suppress proliferation of both human and mouse glioblastoma and neuroblastoma cells without inducing apoptosis. Moreover, short hairpin RNA-mediated knockdown of the basal expression levels of NR5A2 in glioblastoma cells promotes their cell cycle progression. The antiproliferative effect of NR5A2 is mediated by the transcriptional induction of negative regulators of the cell cycle, CDKN1A (encoding for p21cip1), CDKN1B (encoding for p27kip1) and Prox1 Interestingly, two well-established agonists of NR5A2, dilauroyl phosphatidylcholine (DLPC) and diundecanoyl phosphatidylcholine, are able to mimic the antiproliferative action of NR5A2 in human glioblastoma cells via the induction of the same critical genes. Most importantly, treatment with DLPC inhibits glioblastoma tumor growth in vivo in heterotopic and orthotopic xenograft mouse models. These data indicate a tumor suppressor role of NR5A2 in the nervous system and render this nuclear receptor a potential pharmacological target for the treatment of nervous tissue-related tumors.
Τίτλος πηγής δημοσίευσης:	Proceedings of the National Academy of Sciences of the United States of America
Τόμος/Κεφάλαιο:	118
Τεύχος:	39
Σελίδες:	e2015243118
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Κυτταρολογία[EN] Cytology [EL] Χημική Βιολογία[EN] Chemical Biology [EL] Βιοχημεία[EN] Biochemistry [EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology
Λέξεις-Κλειδιά:	LRH1 Agonists Glioblastoma Neuroblastoma Proliferation Animals Cell Cycle Cell Line, Tumor Cell Proliferation Glioblastoma Humans Kaplan-Meier Estimate Mice, SCID Nervous System Neoplasms Neural Stem Cells Neuroblastoma Phosphatidylcholines Receptors, Cytoplasmic and Nuclear Xenograft Model Antitumor Assays
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2021 National Academy of Sciences
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.pnas.org/doi/10.1073/pnas.2015243118
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.pnas.org/
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο