Pharmacologic Inhibition of Ezrin-Radixin-Moesin Phosphorylation is a Novel Therapeutic Strategy in Rhabdomyosarcoma
Joint Authors
Proudfit, Austin
Bhunia, Nabanita
Pore, Debasis
Parker, Yvonne
Lindner, Daniel
Gupta, Neetu
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-09-09
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Intermediate and high-risk rhabdomyosarcoma (RMS) patients have poor prognosis with available treatment options, highlighting a clear unmet need for identification of novel therapeutic strategies.
Ezrin-radixin-moesin (ERM) family members are membrane-cytoskeleton linker proteins with well-defined roles in tumor metastasis, growth, and survival.
ERM protein activity is regulated by dynamic changes in the phosphorylation at a conserved threonine residue in their C-terminal actin-binding domain.
Interestingly, ERM family member, ezrin, has elevated expression in the RMS tissue.
Despite this, the translational scope of targeting ERM family proteins in these tumors through pharmacological inhibition has never been considered.
This study investigates the inhibition of ERM phosphorylation using a small molecule pharmacophore NSC668394 as a potential strategy against RMS.
Upon in vitro treatment with NSC668394, RMS cells exhibit a dose-dependent decrease in cell viability and proliferation, with induction of caspase-3 cleavage and apoptosis.
siRNA-mediated knockdown of individual ERM protein expression revealed that each regulates RMS survival to a different degree.
In vivo administration of NSC668394 in RMS xenografts causes significant decrease in tumor growth, with no adverse effect on body weight.
Collectively, this study highlights the importance of the active conformation of ERM proteins in RMS progression and survival and supports pharmacologic inhibition of these proteins as a novel therapeutic approach.
American Psychological Association (APA)
Proudfit, Austin& Bhunia, Nabanita& Pore, Debasis& Parker, Yvonne& Lindner, Daniel& Gupta, Neetu. 2020. Pharmacologic Inhibition of Ezrin-Radixin-Moesin Phosphorylation is a Novel Therapeutic Strategy in Rhabdomyosarcoma. Complexity،Vol. 2020, no. 2020, pp.1-11.
https://search.emarefa.net/detail/BIM-1207370
Modern Language Association (MLA)
Proudfit, Austin…[et al.]. Pharmacologic Inhibition of Ezrin-Radixin-Moesin Phosphorylation is a Novel Therapeutic Strategy in Rhabdomyosarcoma. Complexity No. 2020 (2020), pp.1-11.
https://search.emarefa.net/detail/BIM-1207370
American Medical Association (AMA)
Proudfit, Austin& Bhunia, Nabanita& Pore, Debasis& Parker, Yvonne& Lindner, Daniel& Gupta, Neetu. Pharmacologic Inhibition of Ezrin-Radixin-Moesin Phosphorylation is a Novel Therapeutic Strategy in Rhabdomyosarcoma. Complexity. 2020. Vol. 2020, no. 2020, pp.1-11.
https://search.emarefa.net/detail/BIM-1207370
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1207370