Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.4300
DC FieldValue
dc.titleFunctional relevance of a six mesenchymal gene signature in epithelial-mesenchymal transition (EMT) reversal by the triple angiokinase inhibitor, nintedanib (BIBF1120)
dc.contributor.authorHuang, R.Y.-J
dc.contributor.authorKuay, K.T
dc.contributor.authorTan, T.Z
dc.contributor.authorAsad, M
dc.contributor.authorTang, H.M
dc.contributor.authorChun Ng, A.H
dc.contributor.authorYe, J
dc.contributor.authorChung, V.Y
dc.contributor.authorThiery, J.P
dc.date.accessioned2020-09-03T10:37:40Z
dc.date.available2020-09-03T10:37:40Z
dc.date.issued2015
dc.identifier.citationHuang, R.Y.-J, Kuay, K.T, Tan, T.Z, Asad, M, Tang, H.M, Chun Ng, A.H, Ye, J, Chung, V.Y, Thiery, J.P (2015). Functional relevance of a six mesenchymal gene signature in epithelial-mesenchymal transition (EMT) reversal by the triple angiokinase inhibitor, nintedanib (BIBF1120). Oncotarget 6 (26) : 22098-22113. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.4300
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174142
dc.description.abstractEpithelial-mesenchymal transition (EMT), a crucial mechanism in carcinoma progression, describes the process whereby epithelial cells lose their apico-basal polarity and junctional complexes and acquire a mesenchymal-like morphology. Several markers are considered to be authentic indicators of an epithelial or mesenchymal status; however, there is currently no comprehensive or systematic method with which to determine their functional relevance. Previously, we identified a 33-gene EMT signature comprising 25 epithelial and 6 mesenchymal genes that best describe this concept of the EMT spectrum. Here, we designed small-scale siRNA screens targeting these six mesenchymal signature genes (CD99L2, EMP3, ITGA5, SYDE1, VIM, ZEB1) to explore their functional relevance and their roles during EMT reversal by nintedanib (BIBF1120) in a mesenchymal-like SKOV3 ovarian cancer cell line. We found that neither cell proliferation nor cytotoxicity was affected by silencing any of these genes. SKOV3 cells expressing siRNA against mesenchymal genes (ZEB1, EMP3, CD99L2, ITGA5, and SYDE1) showed enhanced colony compaction (reduced inter-nuclear distance). Inductions of E-cadherin expression were only observed in SYDE1- and ZEB1-silenced SKOV3 cells. In addition, only SYDE1-silenced SKOV3 cells showed increased anoikis. Finally, we identified that SYDE1 and ZEB1 were down-regulated in nintedanib-treated SKOV3 cells and SYDE1- and ZEB1-silenced SKOV3 cells showed enhanced nintedanib-induced up-regulation of E-cadherin. Nintedanib-treated SKOV3 cells also showed colony compaction and decreases in EMT scores both in vitro and in vivo. We conclude that SYDE1 and ZEB1 are functionally relevant in EMT reversal. This study thus provides a proof-of-concept for the use of in vitro siRNA screening to explore the EMT-related functions of selected genes and their potential relevance in the discovery of EMT reversing drugs.
dc.sourceUnpaywall 20200831
dc.subjectnintedanib
dc.subjectsaracatinib
dc.subjectsmall interfering RNA
dc.subjecttranscription factor ZEB1
dc.subjectuvomorulin
dc.subjectantineoplastic agent
dc.subjectenzyme inhibitor
dc.subjectindole derivative
dc.subjectnintedanib
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantineoplastic activity
dc.subjectArticle
dc.subjectCD99L2 gene
dc.subjectcell proliferation
dc.subjectcontrolled study
dc.subjectcytotoxicity
dc.subjectdown regulation
dc.subjectEMP3 gene
dc.subjectepithelial mesenchymal transition
dc.subjectfemale
dc.subjectgene
dc.subjectgene expression
dc.subjectgene identification
dc.subjectgene silencing
dc.subjecthuman
dc.subjecthuman cell
dc.subjectin vitro study
dc.subjectin vivo study
dc.subjectITGA5 gene
dc.subjectmouse
dc.subjectnonhuman
dc.subjectovarian cancer cell line
dc.subjectprotein expression
dc.subjectSYDE1 gene
dc.subjectupregulation
dc.subjectVIM gene
dc.subjectZEB1 gene
dc.subjectanimal
dc.subjectBagg albino mouse
dc.subjectdrug effects
dc.subjectepithelial mesenchymal transition
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectnude mouse
dc.subjectOvarian Neoplasms
dc.subjectpathology
dc.subjecttreatment outcome
dc.subjecttumor cell line
dc.subjectAnimals
dc.subjectAntineoplastic Agents
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectEnzyme Inhibitors
dc.subjectEpithelial-Mesenchymal Transition
dc.subjectFemale
dc.subjectHumans
dc.subjectIndoles
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectMice, Nude
dc.subjectOvarian Neoplasms
dc.subjectTreatment Outcome
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.description.doi10.18632/oncotarget.4300
dc.description.sourcetitleOncotarget
dc.description.volume6
dc.description.issue26
dc.description.page22098-22113
Appears in Collections:Elements
Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_18632_oncotarget_4300.pdf3.42 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


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