Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.13485
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dc.titleMolecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma
dc.contributor.authorGarg, M
dc.contributor.authorKanojia, D
dc.contributor.authorMayakonda, A
dc.contributor.authorSaid, J.W
dc.contributor.authorDoan, N.B
dc.contributor.authorChien, W
dc.contributor.authorGanesan, T.S
dc.contributor.authorChuang, L.S.H
dc.contributor.authorVenkatachalam, N
dc.contributor.authorBaloglu, E
dc.contributor.authorShacham, S
dc.contributor.authorKauffman, M
dc.contributor.authorKoeffler, H.P
dc.date.accessioned2020-09-09T01:21:13Z
dc.date.available2020-09-09T01:21:13Z
dc.date.issued2017
dc.identifier.citationGarg, M, Kanojia, D, Mayakonda, A, Said, J.W, Doan, N.B, Chien, W, Ganesan, T.S, Chuang, L.S.H, Venkatachalam, N, Baloglu, E, Shacham, S, Kauffman, M, Koeffler, H.P (2017). Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma. Oncotarget 8 (5) : 7521-7532. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.13485
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174903
dc.description.abstractExportin-1 mediates nuclear export of multiple tumor suppressor and growth regulatory proteins. Aberrant expression of exportin-1 is noted in human malignancies, resulting in cytoplasmic mislocalization of its target proteins. We investigated the efficacy of selinexor against liposarcoma cells both in vitro and in vivo. Exportin-1 was highly expressed in liposarcoma samples and cell lines as determined by immunohistochemistry, western blot, and immunofluorescence assay. Knockdown of endogenous exportin-1 inhibited proliferation of liposarcoma cells. Selinexor also significantly decreased cell proliferation as well as induced cell cycle arrest and apoptosis of liposarcoma cells. The drug also significantly decreased tumor volumes and weights of liposarcoma xenografts. Importantly, selinexor inhibited insulin-like growth factor 1 (IGF1) activation of IGF-1R/AKT pathway through upregulation of insulin-like growth factor binding protein 5 (IGFBP5). Further, overexpression and knockdown experiments showed that IGFBP5 acts as a tumor suppressor and its expression was restored upon selinexor treatment of liposarcoma cells. Selinexor decreased aurora kinase A and B levels in these cells and inhibitors of these kinases suppressed the growth of the liposarcoma cells. Overall, our study showed that selinexor treatment restored tumor suppressive function of IGFBP5 and inhibited aurora kinase A and B in liposarcoma cells supporting the usefulness of selinexor as a potential therapeutic strategy for the treatment of this cancer.
dc.publisherImpact Journals LLC
dc.sourceUnpaywall 20200831
dc.subjectexportin 1
dc.subjectprotein kinase B
dc.subjectselinexor
dc.subjectsomatomedin binding protein 5
dc.subjectsomatomedin C
dc.subjectsomatomedin C receptor
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcancer inhibition
dc.subjectcell cycle arrest
dc.subjectcell proliferation
dc.subjectcontrolled study
dc.subjectdrug efficacy
dc.subjecthuman
dc.subjecthuman cell
dc.subjectimmunofluorescence test
dc.subjectliposarcoma
dc.subjectliposarcoma cell
dc.subjectmale
dc.subjectmolecular dynamics
dc.subjectmouse
dc.subjectnonhuman
dc.subjectprotein expression
dc.subjecttumor volume
dc.subjecttumor xenograft
dc.subjectupregulation
dc.subjectWestern blotting
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.18632/oncotarget.13485
dc.description.sourcetitleOncotarget
dc.description.volume8
dc.description.issue5
dc.description.page7521-7532
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