scholarly journals IGF2BP1 is a targetable SRC/MAPK-dependent driver of invasive growth in ovarian cancer

2020 ◽  
Author(s):  
Nadine Bley ◽  
Annekatrin Schott ◽  
Simon Müller ◽  
Danny Misiak ◽  
Marcell Lederer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Rna Binding ◽  
3D Culture ◽  
Adherens Junction ◽  
Ovarian Cancer Cells ◽  
Invasive Growth ◽  
Dependent Manner ◽  
Mesenchymal Transition

AbstractEpithelial-to-mesenchymal transition (EMT) is a hallmark of aggressive, mesenchymal-like high-grade serous ovarian carcinoma (HG-SOC). The SRC kinase is a key driver of cancer-associated EMT promoting adherens junction (AJ) disassembly by phosphorylation-driven internalization and degradation of AJ proteins. Here we show, that the IGF2 mRNA binding protein 1 (IGF2BP1) is up-regulated in mesenchymal-like HG-SOC and promotes SRC activation by a previously unknown protein-ligand-induced, but RNA-independent mechanism. IGF2BP1-driven invasive growth of ovarian cancer cells essentially relies on the SRC-dependent disassembly of AJs. Concomitantly, IGF2BP1 enhances ERK2 expression in a RNA-binding dependent manner. Together this reveals a post-transcriptional mechanism of interconnected stimulation of SRC/ERK signaling in ovarian cancer cells. The IGF2BP1-SRC/ERK2 axis is targetable by the SRC-inhibitor saracatinib and MEK-inhibitor selumetinib. However, due to IGF2BP1-directed stimulation only combinatorial treatment effectively overcomes the IGF2BP1-promoted invasive growth in 3D culture conditions as well as intraperitoneal mouse models. In conclusion, we reveal an unexpected role of IGF2BP1 in enhancing SRC/MAPK-driven invasive growth of ovarian cancer cells. This provides a rational for the therapeutic benefit of combinatorial SRC/MEK inhibition in mesenchymal-like HG-SOC.Graphical Abstract

scholarly journals Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Huan Lu ◽  
Guanlin Zheng ◽  
Xiang Gao ◽  
Chanjuan Chen ◽  
Min Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Rna Binding ◽  
Erk Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Vacuolar Protein

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

scholarly journals Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells

2017 ◽  
Vol 8 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Wenying Huo ◽  
Guannan Zhao ◽  
Jinggang Yin ◽  
Xuan Ouyang ◽  
Yinan Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Gene Editing ◽  
Epithelial To Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition

scholarly journals EZH2 inhibition promotes epithelial-to-mesenchymal transition in ovarian cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (51) ◽  
pp. 84453-84467 ◽  
Author(s):  
Horacio Cardenas ◽  
Janice Zhao ◽  
Edyta Vieth ◽  
Kenneth P. Nephew ◽  
Daniela Matei
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition

scholarly journals Wnt5A and TGFβ1 Converges through YAP1 Activity and Integrin Alpha v Up-Regulation Promoting Epithelial to Mesenchymal Transition in Ovarian Cancer Cells and Mesothelial Cell Activation

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 237
Author(s):  
Zeinab Dehghani-Ghobadi ◽  
Shahrzad Sheikh Hasani ◽  
Ehsan Arefian ◽  
Ghamartaj Hossein
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Serous Ovarian Cancer ◽  
Mesenchymal Transition ◽  
Nuclear Shuttling

In this paper, we investigate whether Wnt5A is associated with the TGF-β1/Smad2/3 and Hippo-YAP1/TAZ-TEAD pathways, implicated in epithelial to mesenchymal transition (EMT) in epithelial ovarian cancer. We used 3D and 2D cultures of human epithelial ovarian cancer cell lines SKOV-3, OVCAR-3, CAOV-4, and different subtypes of human serous ovarian cancer compared to normal ovary specimens. Wnt5A showed a positive correlation with TAZ and TGFβ1 in high- and low-grade serous ovarian cancer specimens compared to borderline serous and normal ovaries. Silencing Wnt5A by siRNAs significantly decreased Smad2/3 activation and YAP1 expression and nuclear shuttling in ovarian cancer (OvCa) cells. Furthermore, Wnt5A was required for TGFβ1-induced cell migration and invasion. In addition, inhibition of YAP1 transcriptional activity by Verteporfin (VP) altered OvCa cell migration and invasion through decreased Wnt5A expression and inhibition of Smad2/3 activation, which was reverted in the presence of exogenous Wnt5A. We found that the activation of TGFβ1 and YAP1 nuclear shuttling was promoted by Wnt5A-induced integrin alpha v. Lastly, Wnt5A was implicated in activating human primary omental mesothelial cells and subsequent invasion of ovarian cancer cells. Together, we propose that Wnt5A could be a critical mediator of EMT-associated pathways.

scholarly journals Novel oncogenic and chemoresistance-inducing functions of resistin in ovarian cancer cells require miRNAs-mediated induction of epithelial-to-mesenchymal transition

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ling Qiu ◽  
Guo-Feng Zhang ◽  
Lei Yu ◽  
Hong-Yong Wang ◽  
Xiao-Jing Jia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition

scholarly journals Knockout of MTF1 Inhibits the Epithelial to Mesenchymal Transition in Ovarian Cancer Cells

2018 ◽  
Vol 9 (24) ◽  
pp. 4578-4585 ◽  
Author(s):  
Liang Ji ◽  
Guannan Zhao ◽  
Peng Zhang ◽  
Wenying Huo ◽  
Peixin Dong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition

scholarly journals Emodin inhibits epithelial to mesenchymal transition in epithelial ovarian cancer cells by regulation of GSK-3β/β-catenin/ZEB1 signaling pathway

2016 ◽  
Vol 35 (4) ◽  
pp. 2027-2034 ◽  
Author(s):  
CHEN HU ◽  
TAOTAO DONG ◽  
RUI LI ◽  
JINGJING LU ◽  
XUAN WEI ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Gsk 3Β

scholarly journals Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelial to mesenchymal transition in ovarian cancer cells

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94666-94680 ◽  
Author(s):  
Guannan Zhao ◽  
Qinghui Wang ◽  
Qingqing Gu ◽  
Wenan Qiang ◽  
Jian-Jun Wei ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition
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