Please use this identifier to cite or link to this item:
Title: Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma
Authors: Garg, 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 
Keywords: exportin 1
protein kinase B
somatomedin binding protein 5
somatomedin C
somatomedin C receptor
animal experiment
animal model
animal tissue
cancer inhibition
cell cycle arrest
cell proliferation
controlled study
drug efficacy
human cell
immunofluorescence test
liposarcoma cell
molecular dynamics
protein expression
tumor volume
tumor xenograft
Western blotting
Issue Date: 2017
Publisher: Impact Journals LLC
Citation: Garg, 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.
Abstract: Exportin-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.
Source Title: Oncotarget
ISSN: 19492553
DOI: 10.18632/oncotarget.13485
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_18632_oncotarget_13485.pdf5.04 MBAdobe PDF



Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.