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Article: Targeting Dopamine Receptor D2 by Imipridone Suppresses Uterine Serous Cancer Malignant Phenotype

TitleTargeting Dopamine Receptor D2 by Imipridone Suppresses Uterine Serous Cancer Malignant Phenotype
Authors
Keywordsuterine serous cancer
imipridone
dopamine receptor D2
metabolic reprogramming
Issue Date2020
PublisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/
Citation
Cancers, 2020, v. 12, p. article no. 2436 How to Cite?
AbstractUterine serous cancer (USC) is an aggressive subtype of endometrial cancer, with poor survival and high recurrence rates. The development of novel and effective therapies specific to USC would aid in its management. However, few studies have focused solely on this rare subtype. The current study demonstrated that the orally bioavailable, investigational new drug and novel imipridone ONC206 suppressed USC cell proliferation and induced apoptosis both in vitro and in vivo. Disruption of the DRD2-mediated p38MAPK/ERK/PGC-1α network by ONC206 led to metabolic reprogramming and suppression of both glycolysis and oxidative phosphorylation. ONC206 also synergized with paclitaxel in reducing USC cell viability. In addition, DRD2 overexpression correlated with poor overall survival in patients. This study provides the first evidence that ONC206 induced metabolic reprogramming in USC cells and is a promising therapeutic agent for USC treatment. These findings support further development of ONC206 as a promising therapeutic agent and improves survival rates in patients with USC.
Persistent Identifierhttp://hdl.handle.net/10722/300864
ISSN
2023 Impact Factor: 4.5
2023 SCImago Journal Rankings: 1.391
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, W-
dc.contributor.authorZhang, L-
dc.contributor.authorFerri-Borgogno, S-
dc.contributor.authorKwan, SY-
dc.contributor.authorLewis, KE-
dc.contributor.authorCun, HT-
dc.contributor.authorYeung, TL-
dc.contributor.authorSoliman, PT-
dc.contributor.authorTarapore, RS-
dc.contributor.authorAllen, JE-
dc.contributor.authorGuan, X-
dc.contributor.authorLu, KH-
dc.contributor.authorMok, SC-
dc.contributor.authorAu-Yeung, CL-
dc.date.accessioned2021-07-06T03:11:16Z-
dc.date.available2021-07-06T03:11:16Z-
dc.date.issued2020-
dc.identifier.citationCancers, 2020, v. 12, p. article no. 2436-
dc.identifier.issn2072-6694-
dc.identifier.urihttp://hdl.handle.net/10722/300864-
dc.description.abstractUterine serous cancer (USC) is an aggressive subtype of endometrial cancer, with poor survival and high recurrence rates. The development of novel and effective therapies specific to USC would aid in its management. However, few studies have focused solely on this rare subtype. The current study demonstrated that the orally bioavailable, investigational new drug and novel imipridone ONC206 suppressed USC cell proliferation and induced apoptosis both in vitro and in vivo. Disruption of the DRD2-mediated p38MAPK/ERK/PGC-1α network by ONC206 led to metabolic reprogramming and suppression of both glycolysis and oxidative phosphorylation. ONC206 also synergized with paclitaxel in reducing USC cell viability. In addition, DRD2 overexpression correlated with poor overall survival in patients. This study provides the first evidence that ONC206 induced metabolic reprogramming in USC cells and is a promising therapeutic agent for USC treatment. These findings support further development of ONC206 as a promising therapeutic agent and improves survival rates in patients with USC.-
dc.languageeng-
dc.publisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/-
dc.relation.ispartofCancers-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectuterine serous cancer-
dc.subjectimipridone-
dc.subjectdopamine receptor D2-
dc.subjectmetabolic reprogramming-
dc.titleTargeting Dopamine Receptor D2 by Imipridone Suppresses Uterine Serous Cancer Malignant Phenotype-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/cancers12092436-
dc.identifier.pmid32867127-
dc.identifier.pmcidPMC7563948-
dc.identifier.scopuseid_2-s2.0-85092331153-
dc.identifier.hkuros323265-
dc.identifier.volume12-
dc.identifier.spagearticle no. 2436-
dc.identifier.epagearticle no. 2436-
dc.identifier.isiWOS:000579947900001-
dc.publisher.placeSwitzerland-

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