Impact of intercellular connectivity on epithelial mesenchymal transition plasticity

Mandal, Mousumi; Ghosh, Biswajoy; Rajput, Monika; Chatterjee, Jyotirmoy

doi:10.1016/j.bbamcr.2020.118784

Cited by 9 publications

(9 citation statements)

References 87 publications

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“…Given that EMP often involves changes in cellular morphology, an EMP continuum in the morphological landscape is also being increasingly characterised [Leggett et al, 2016;Devaraj and Bose, 2019]. The trajectories of individual cells in these EMP landscape(s) need not be a cell-autonomous phenomenon; they can be influenced by various biophysical and biochemical modes of cell-cell communication [Mandal et al, 2020;Tripathi et al, 2020b] and by microenvironment-specific conditions such as hypoxia, acidity and nutritional levels that may vary considerably across a single tumour and can also influence movement along the EMP axis [Williams et al, 2019]. Novel analytical tools with single cell RNA-se-Fig.…”

mentioning

confidence: 99%

Measuring and Modelling the Epithelial- Mesenchymal Hybrid State in Cancer: Clinical Implications

Jolly

Murphy

Bhatia

et al. 2021

Cells Tissues Organs

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The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity (EMP). We review here evidence for the presence, prognostic significance, and therapeutic potential of the E/M hybrid state in carcinoma. We further assess modelling predictions and validation studies to demonstrate stabilised E/M hybrid states along the spectrum of EMP, as well as computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based techniques.

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mentioning

confidence: 99%

Measuring and Modelling the Epithelial- Mesenchymal Hybrid State in Cancer: Clinical Implications

Jolly

Murphy

Bhatia

et al. 2021

Cells Tissues Organs

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“…The potential of cancer cells to form nanobridges with endothelial cells is correlated with its metastatic potential . Researchers have speculated that EMT progression stimulates the formation of nanoscale membrane bridges like tunneling nanotubes (TNTs) . Sengupta and co-workers have performed siRNA-mediated knockdown of a protein of the exocyst that is involved in such TNT formation.…”

Section: Resultsmentioning

confidence: 97%

“…58 Researchers have speculated that EMT progression stimulates the formation of nanoscale membrane bridges like tunneling nanotubes (TNTs). 60 Sengupta and co-workers have performed siRNAmediated knockdown of a protein of the exocyst that is involved in such TNT formation. They observed a decrease in the population of TNTs.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Harnessing Peptide-Functionalized Multivalent Gold Nanorods for Promoting Enhanced Gene Silencing and Managing Breast Cancer Metastasis

Chakraborty

Biswas

Mishra

et al. 2023

ACS Appl. Bio Mater.

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Small interfering RNA (siRNA) has become the cornerstone against undruggable targets and for managing metastatic breast cancer. However, an effective gene silencing approach is faced with a major challenge due to the delivery problem. In our present study, we have demonstrated efficient siRNA delivery, superior gene silencing, and inhibition of metastasis in triple-negative breast cancer cells (MDA-MB-231) using rod-shaped (aspect ratio: 4) multivalent peptide-functionalized gold nanoparticles and compared them to monovalent free peptide doses. Multivalency is a new concept in biology, and tuning the physical parameters of multivalent nanoparticles can enhance gene silencing and antitumor efficacy. We explored the effect of the multivalency of shape- and size-dependent peptide-functionalized gold nanoparticles in siRNA delivery. Our study demonstrates that peptide functionalization leads to reduced toxicity of the nanoparticles. Such designed peptide-functionalized nanorods also demonstrate antimetastatic efficacy in Notch1-silenced cells by preventing EMT progression in vitro. We have shown siRNA delivery in the hard-to-transfect primary cell line HUVEC and also demonstrated that the Notch1-silenced MDA-MB-231 cell line has failed to form nanobridge-mediated foci with the HUVEC in the co-culture of HUVEC and MDA-MB-231, which promote metastasis. This antimetastatic effect is further checked in a xenotransplant in vivo zebrafish model. In vivo studies also suggest that our designed nanoparticles mediated inhibition of micrometastasis due to silencing of the Notch1 gene. The outcome of our study highlights that the structure–activity relationship of multifunctional nanoparticles can be harnessed to modulate their biological activity.

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“…Devaraj and Bose recently quantified the phenotypic transitions of epidermal growth factor (EGF)-induced EMT based on the morphological characteristics of individual cells, specifically distinct cellular shapes (Devaraj & Bose, 2019). Mandal and colleagues defined distinct morphological features of both cells and intercellular connections during EMT and characterized the progression between these different morphological states (Mandal et al, 2016, 2020). Similar to these prior works, we implement feature extraction directly into the pipeline.…”

Section: Discussionmentioning

confidence: 99%

Immunofluorescence Image Feature Analysis and Phenotype Scoring Pipeline for Distinguishing Epithelial–Mesenchymal Transition

et al. 2021

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Impact of intercellular connectivity on epithelial mesenchymal transition plasticity

Cited by 9 publications

References 87 publications

Measuring and Modelling the Epithelial- Mesenchymal Hybrid State in Cancer: Clinical Implications

Measuring and Modelling the Epithelial- Mesenchymal Hybrid State in Cancer: Clinical Implications

Harnessing Peptide-Functionalized Multivalent Gold Nanorods for Promoting Enhanced Gene Silencing and Managing Breast Cancer Metastasis

Immunofluorescence Image Feature Analysis and Phenotype Scoring Pipeline for Distinguishing Epithelial–Mesenchymal Transition

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