scholarly journals A flexible network of Vimentin intermediate filaments promotes the migration of amoeboid cancer cells through confined environments

2019 ◽  
Author(s):  
Sara M. Tudor ◽  
Sandrine B. Lavenus ◽  
Jeremy S. Logue
Keyword(s):  
Mechanical Properties ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Human Cancer ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Human Cancer Cells ◽  
Cell Mechanical Properties ◽  
Metastasis Inhibitor

AbstractThe spread of tumor cells to distant sites is promoted by their ability to switch between mesenchymal and amoeboid (bleb-based) migration. Because of this, inhibitors of metastasis must account for each motility mode. To this end, here we determine the precise role of the Vimentin intermediate filament system in regulating the migration of amoeboid human cancer cells. Vimentin is a classic marker of epithelial to mesenchymal transition and is therefore, an ideal target for a metastasis inhibitor. However, the role of Vimentin in amoeboid migration has not been determined. Since amoeboid, leader bleb-based migration occurs in confined spaces and Vimentin is known to be a major determinant of cell mechanical properties, we hypothesized that a flexible Vimentin network is required for fast amoeboid migration. This was tested using our PDMS slab-based approach for the confinement of cells, RNAi, over-expression, pharmacological treatments, and measurements of cell stiffness. In contrast to Vimentin RNAi, inducing the bundling of Vimentin was found to inhibit fast amoeboid migration and proliferation. Importantly, these effects were independent of changes in actomyosin contractility. Collectively, our data supports a model whereby the perturbation of cell mechanical properties by Vimentin bundling inhibits the invasive properties of cancer cells.

scholarly journals A flexible network of vimentin intermediate filaments promotes migration of amoeboid cancer cells through confined environments

2020 ◽  
Vol 295 (19) ◽  
pp. 6700-6709 ◽  
Author(s):  
Sandrine B. Lavenus ◽  
Sara M. Tudor ◽  
Maria F. Ullo ◽  
Karl W. Vosatka ◽  
Jeremy S. Logue
Keyword(s):  
Mechanical Properties ◽  
Cancer Cells ◽  
Intermediate Filament ◽  
Epithelial To Mesenchymal Transition ◽  
Human Cancer ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cell Mechanical Properties ◽  
Vimentin Intermediate Filament

Tumor cells can spread to distant sites through their ability to switch between mesenchymal and amoeboid (bleb-based) migration. Because of this difference, inhibitors of metastasis must account for each migration mode. However, the role of vimentin in amoeboid migration has not been determined. Because amoeboid leader bleb–based migration (LBBM) occurs in confined spaces and vimentin is known to strongly influence cell-mechanical properties, we hypothesized that a flexible vimentin network is required for fast amoeboid migration. To this end, here we determined the precise role of the vimentin intermediate filament system in regulating the migration of amoeboid human cancer cells. Vimentin is a classic marker of epithelial-to-mesenchymal transition and is therefore an ideal target for a metastasis inhibitor. Using a previously developed polydimethylsiloxane slab–based approach to confine cells, RNAi-based vimentin silencing, vimentin overexpression, pharmacological treatments, and measurements of cell stiffness, we found that RNAi-mediated depletion of vimentin increases LBBM by ∼50% compared with control cells and that vimentin overexpression and simvastatin-induced vimentin bundling inhibit fast amoeboid migration and proliferation. Importantly, these effects were independent of changes in actomyosin contractility. Our results indicate that a flexible vimentin intermediate filament network promotes LBBM of amoeboid cancer cells in confined environments and that vimentin bundling perturbs cell-mechanical properties and inhibits the invasive properties of cancer cells.

The small molecule SI113 hinders epithelial‐to‐mesenchymal transition and subverts cytoskeletal organization in human cancer cells

2019 ◽  
Vol 234 (12) ◽  
pp. 22529-22542 ◽  
Author(s):  
Claudia Abbruzzese ◽  
Silvia Matteoni ◽  
Michele Persico ◽  
Barbara Ascione ◽  
Silvia Schenone ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Small Molecule ◽  
Epithelial To Mesenchymal Transition ◽  
Human Cancer ◽  
Cytoskeletal Organization ◽  
Mesenchymal Transition ◽  
Human Cancer Cells

The Role of Sensing Peptides in the Cross-talk between Microbiota and Human Cancer Cells

2018 ◽  
Vol 18 (18) ◽  
pp. 1567-1571
Author(s):  
Anna Lucia Tornesello ◽  
Luigi Buonaguro ◽  
Maria Lina Tornesello ◽  
Franco M. Buonaguro
Keyword(s):  
Cancer Cells ◽  
Cross Talk ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
The Cross

scholarly journals Human Cancer Cells Express Slug-based Epithelial-Mesenchymal Transition Gene Signature Obtained in Vivo

2011 ◽  
Author(s):  
Jessica Kandel ◽  
Dimitris Anastassiou ◽  
Viktoria Rumjantseva ◽  
Wei-yi Cheng ◽  
Jianzhong Huang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Gene Signature ◽  
Mesenchymal Transition ◽  
Human Cancer Cells

scholarly journals Role of tight junctions in the epithelial-to-mesenchymal transition of cancer cells

2020 ◽  
pp. 183503 ◽  
Author(s):  
Daisuke Kyuno ◽  
Akira Takasawa ◽  
Shin Kikuchi ◽  
Ichiro Takemasa ◽  
Makoto Osanai ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tight Junctions ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals EMT reversal in human cancer cells after IR knockdown in hyperinsulinemic mice

2016 ◽  
Vol 23 (9) ◽  
pp. 747-758 ◽  
Author(s):  
Zara Zelenko ◽  
Emily Jane Gallagher ◽  
Irini Markella Antoniou ◽  
Deepali Sachdev ◽  
Anupma Nayak ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Mortality Data ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Insulin Resistant ◽  
Human Cancer Cells

Type 2 diabetes (T2D) is associated with increased cancer risk and cancer-related mortality. Data herein show that we generated an immunodeficient hyperinsulinemic mouse by crossing theRag1−/−mice, which have no mature B or T lymphocytes, with the MKR mouse model of T2D to generate theRag1−/−(Rag/WT) andRag1−/−/MKR+/+(Rag/MKR) mice. The female Rag/MKR mice are insulin resistant and have significantly higher nonfasting plasma insulin levels compared with the Rag/WT controls. Therefore, we used these Rag/MKR mice to investigate the role of endogenous hyperinsulinemia on human cancer progression. In this study, we show that hyperinsulinemia in the Rag/MKR mice increases the expression of mesenchymal transcription factors,TWIST1andZEB1, and increases the expression of the angiogenesis marker, vascular endothelial growth factor A (VEGFA). We also show that silencing the insulin receptor (IR) in the human LCC6 cancer cells leads to decreased tumor growth and metastases, suppression of mesenchymal markers vimentin, SLUG, TWIST1 and ZEB1, suppression of angiogenesis markers,VEGFAandVEGFD, and re-expression of the epithelial marker, E-cadherin. The data in this paper demonstrate that IR knockdown in primary tumors partially reverses the growth-promoting effects of hyperinsulinemia as well as highlighting the importance of the insulin receptor signaling pathway in cancer progression, and more specifically in epithelial–mesenchymal transition.

scholarly journals In-Situ Description of the Role of PtdIns(3,4,5)P3 and PtdSer on PDK1 Regulation in Human Cancer Cells by Advanced Quantitative Microscopy

2014 ◽  
Vol 106 (2) ◽  
pp. 522a-523a
Author(s):  
Gloria de las Heras ◽  
Veronique Calleja ◽  
Banafshe Larijani ◽  
Jose Requejo-Isidro
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Quantitative Microscopy ◽  
Human Cancer Cells

MicroRNA-21 inhibitor potentiates anti-tumor effect of radiation therapy in vitro and in vivo

2014 ◽  
Vol 2 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Bong Jun Cho ◽  
Hans H. Kim ◽  
David J Lee ◽  
Eun Jung Choi ◽  
Yeo Hyun Hwang ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Combined Treatment ◽  
A549 Cells ◽  
Specific Inhibitor ◽  
Tumor Burden ◽  
Mesenchymal Transition ◽  
Human Cancer Cells

AbstractMicroRNA-21 (miR-21) plays important roles in carcinogenesis and is highly expressed in diverse human cancers. We evaluated the potential of targeting miRNA-21 to overcome the radioresistance of human cancer cells having an activated EGFR2-associated signaling and also aimed to elucidate the mechanisms of radiosensitization, and the effect on epithelial- mesenchymal transition (EMT). Ectopic overexpression of miR-21 up-regulated EGFR/HER2-associated signaling and increased radioresistance of a panel of human cancer cells (U251, U87, and A549 cells). In contrast, a specific inhibitor of miR-21 attenuated this signaling and radiosensitized a panel of human cancer cells. Inhibition of miR-21 was associated with persistent γH2AX foci formation. Inhibition of miR-21 decreased the typical features of EMT, such as invasion and migration and vascular tube formation. Treatment with anti-miR-21 decreased tumor burden in nude mice bearing intracranial U251 xenografts compared to controls. Combined treatment of anti-miR-21 and radiation further decreased tumor burden compared to each treatment alone. In summary, miR-21 is an important onco-miR, which confers radioresistance and diverse features of EMT. Inhibition of miR-21 could be a potential strategy for improving the efficacy of radiation therapy via unique modulation of pro-survival signaling implicated in radiation response and EMT.

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