Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.4300
DC Field | Value | |
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dc.title | Functional relevance of a six mesenchymal gene signature in epithelial-mesenchymal transition (EMT) reversal by the triple angiokinase inhibitor, nintedanib (BIBF1120) | |
dc.contributor.author | Huang, R.Y.-J | |
dc.contributor.author | Kuay, K.T | |
dc.contributor.author | Tan, T.Z | |
dc.contributor.author | Asad, M | |
dc.contributor.author | Tang, H.M | |
dc.contributor.author | Chun Ng, A.H | |
dc.contributor.author | Ye, J | |
dc.contributor.author | Chung, V.Y | |
dc.contributor.author | Thiery, J.P | |
dc.date.accessioned | 2020-09-03T10:37:40Z | |
dc.date.available | 2020-09-03T10:37:40Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Huang, 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.issn | 19492553 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/174142 | |
dc.description.abstract | Epithelial-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.source | Unpaywall 20200831 | |
dc.subject | nintedanib | |
dc.subject | saracatinib | |
dc.subject | small interfering RNA | |
dc.subject | transcription factor ZEB1 | |
dc.subject | uvomorulin | |
dc.subject | antineoplastic agent | |
dc.subject | enzyme inhibitor | |
dc.subject | indole derivative | |
dc.subject | nintedanib | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | antineoplastic activity | |
dc.subject | Article | |
dc.subject | CD99L2 gene | |
dc.subject | cell proliferation | |
dc.subject | controlled study | |
dc.subject | cytotoxicity | |
dc.subject | down regulation | |
dc.subject | EMP3 gene | |
dc.subject | epithelial mesenchymal transition | |
dc.subject | female | |
dc.subject | gene | |
dc.subject | gene expression | |
dc.subject | gene identification | |
dc.subject | gene silencing | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | in vitro study | |
dc.subject | in vivo study | |
dc.subject | ITGA5 gene | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | ovarian cancer cell line | |
dc.subject | protein expression | |
dc.subject | SYDE1 gene | |
dc.subject | upregulation | |
dc.subject | VIM gene | |
dc.subject | ZEB1 gene | |
dc.subject | animal | |
dc.subject | Bagg albino mouse | |
dc.subject | drug effects | |
dc.subject | epithelial mesenchymal transition | |
dc.subject | genetics | |
dc.subject | metabolism | |
dc.subject | nude mouse | |
dc.subject | Ovarian Neoplasms | |
dc.subject | pathology | |
dc.subject | treatment outcome | |
dc.subject | tumor cell line | |
dc.subject | Animals | |
dc.subject | Antineoplastic Agents | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cell Proliferation | |
dc.subject | Enzyme Inhibitors | |
dc.subject | Epithelial-Mesenchymal Transition | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Indoles | |
dc.subject | Mice | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | Mice, Nude | |
dc.subject | Ovarian Neoplasms | |
dc.subject | Treatment Outcome | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.contributor.department | DEPT OF BIOCHEMISTRY | |
dc.description.doi | 10.18632/oncotarget.4300 | |
dc.description.sourcetitle | Oncotarget | |
dc.description.volume | 6 | |
dc.description.issue | 26 | |
dc.description.page | 22098-22113 | |
Appears in Collections: | Elements Staff Publications |
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