The multiverse nature of epithelial to mesenchymal transition

Simeone, Pasquale; Trerotola, Marco; Franck, Julien; Cardon, Tristan; Marchisio, Marco; Fournier, Isabelle; Salzet, Michel; Maffia, Michele; Vergara, Daniele

doi:10.1016/j.semcancer.2018.11.004

Cited by 80 publications

(76 citation statements)

References 98 publications

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“…Previous studies reported that Snail, a component of an EMT-related network, increased cellular growth, migration, invasion, and EMT [32]. We obtained similar results in A549 cells ( Fig.…”

Section: The Yap/tead Complex Directly Binds To the Promoter Of Snailsupporting

confidence: 89%

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis

Jin

Guo

et al. 2020

J Exp Clin Cancer Res

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Background: Recent evidence indicates that metformin inhibits mammalian cancer growth and metastasis through the regulation of microRNAs. Metformin regulates miR-381 stability, which plays a vital role in tumor progression. Moreover, increased YAP expression and activity induce non-small cell lung cancer (NSCLC) tumor growth and metastasis. However, the molecular mechanism underpinning how metformin-induced upregulation of miR-381 directly targets YAP or its interactions with the epithelial-mesenchymal transition (EMT) marker protein Snail in NSCLC is still unknown. Methods: Levels of RNA and protein were analyzed using qPCR, western blotting and immunofluorescence staining. Cellular proliferation was detected using a CCK8 assay. Cell migration and invasion were analyzed using wound healing and transwell assays. Promoter activity and transcription were investigated using the luciferase reporter assay. Chromatin immunoprecipitation was used to detect the binding of YAP to the promoter of Snail. The interaction between miR-381 and the 3′UTR of YAP mRNA was analyzed using the MS2 expression system and co-immunoprecipitation with biotin. Results: We observed that miR-381 expression is negatively correlated with YAP expression and plays an opposite role to YAP in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. The miR-381 function as a tumor suppressor was significantly downregulated in lung cancer tissue specimens and cell lines, which decreased the expression of its direct target YAP. In addition, metformin decreased cell growth, migration, invasion, and EMT via up-regulation of miR-381. Moreover, YAP, which functions as a co-transcription factor, enhanced NSCLC progression and metastasis by upregulation of Snail. Snail knockdown downregulated the mesenchymal marker vimentin and upregulated the epithelial marker E-cadherin in lung cancer cells. Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT. Conclusions: Metformin-induced repression of miR-381-YAP-Snail axis activity disrupts NSCLC growth and metastasis. Thus, we believe that the miR-381-YAP-Snail signal axis may be a suitable diagnostic marker and a potential therapeutic target for lung cancer.

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“…Previous studies reported that Snail, a component of an EMT-related network, increased cellular growth, migration, invasion, and EMT [32]. We obtained similar results in A549 cells ( Fig.…”

Section: The Yap/tead Complex Directly Binds To the Promoter Of Snailsupporting

confidence: 89%

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis

Jin

Guo

et al. 2020

J Exp Clin Cancer Res

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“…31 EMT is a cellular transition from an epithelial to a mesenchymal state, which can be regulated at multilayer levels, including transcriptional control of gene expression, regulation of RNA splicing, and translational/ post-translational control. 32 Distinct EMT transition states present different functions, with the hybrid EMT state presenting the highest metastatic potential. 35 EMT plays a vital role in the metastasis of CC, which is a significant phenotypic change through the acquisition of mesenchymal marker proteins (N-cadherin and Vimentin) and the loss of epithelial marker proteins (E-cadherin).…”

Section: Discussionmentioning

confidence: 99%

<p>Long Non-Coding RNA-NEAT1 Promotes Cell Migration and Invasion via Regulating miR-124/NF-κB Pathway in Cervical Cancer</p>

Shen

Zhao

Zhang

et al. 2020

OTT

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Background: This study aimed to investigate the regulatory role of lncRNA-NEAT1 on cervical cancer (CC) and the underlying molecular mechanisms. Methods: The expression of lncRNA-NEAT1 and miR-124 was detected in CC tissues and cells (HeLa and SiHa cells) by qRT-RCR. The relation between lncRNA-NEAT1 expression and clinical parameters of CC patients was explored. The cell migration and invasion were detected by wound healing assay and transwell assay. The cell proliferation was detected by CCK-8 and anchorage-independent colony assay. The targeting relation between miR-124 and lncRNA-NEAT1 was predicted by TargetScan and identified by dual luciferase reporter gene and RNA pull-down assay. The expression of metastasis-(MMP-2 and MMP), EMT-(E-cadherin, N-cadherin and Vimentin), and NF-κB pathway-related factors (NF-κB p65, p-NF-κB p65 and IκBα) was detected by Western blot. Results: The expression of lncRNA-NEAT1 was upregulated in CC tissues and cells and positively correlated with TNM stage and lymph node metastasis. Overexpression of lncRNA-NEAT1 promoted the proliferation, migration and invasion, influenced the expression of EMT markers, and activated NF-κB pathway in HeLa and SiHa cells. Silencing of lncRNA-NEAT1 exhibited opposite effects on HeLa and SiHa cells. LncRNA-NEAT1 could negatively regulate its target miR-124. MiR-124 reversed the effects of lncRNA-NEAT1 on the migration, invasion, EMT and NF-κB pathway of HeLa cells. Conclusion: LncRNA-NEAT1 promoted the migration and invasion of CC cells via regulating miR-124/NF-κB pathway.

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“…In respect to cell physiology, serum removal and anchorage-independent growth is a major change. It mimics an epithelial-to-mesenchymal transition [ 29 , 30 ] which is one of the most complex and multilayer-leveled processes that cells can undergo [ 31 ]. In fact, it is not by chance that principal component analysis identified ‘serum-containing adherent vs. serum-free suspension’ cultures as the first source of variability in the dataset, before cell bank repository origin or CAV-2 infection ( Figure 6 A).…”

Section: Discussionmentioning

confidence: 99%

Cell Bank Origin of MDCK Parental Cells Shapes Adaptation to Serum-Free Suspension Culture and Canine Adenoviral Vector Production

Rodrigues

Fernandes

Laske

et al. 2020

IJMS

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Phenotypic variation in cultured mammalian cell lines is known to be induced by passaging and culture conditions. Yet, the effect these variations have on the production of viral vectors has been overlooked. In this work we evaluated the impact of using Madin–Darby canine kidney (MDCK) parental cells from American Type Culture Collection (ATCC) or European Collection of Authenticated Cell Cultures (ECACC) cell bank repositories in both adherent and suspension cultures for the production of canine adenoviral vectors type 2 (CAV-2). To further explore the differences between cells, we conducted whole-genome transcriptome analysis. ECACC’s MDCK showed to be a less heterogeneous population, more difficult to adapt to suspension and serum-free culture conditions, but more permissive to CAV-2 replication progression, enabling higher yields. Transcriptome data indicated that this increased permissiveness is due to a general down-regulation of biological networks of innate immunity in ECACC cells, including apoptosis and death receptor signaling, Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling, toll-like receptors signaling and the canonical pathway of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. These results show the impact of MDCK source on the outcome of viral-based production processes further elucidating transcriptome signatures underlying enhanced adenoviral replication. Following functional validation, the genes and networks identified herein can be targeted in future engineering approaches aiming at improving the production of CAV-2 gene therapy vectors.

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The multiverse nature of epithelial to mesenchymal transition

Cited by 80 publications

References 98 publications

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis

<p>Long Non-Coding RNA-NEAT1 Promotes Cell Migration and Invasion via Regulating miR-124/NF-κB Pathway in Cervical Cancer</p>

Cell Bank Origin of MDCK Parental Cells Shapes Adaptation to Serum-Free Suspension Culture and Canine Adenoviral Vector Production

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