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Pleural mesothelioma (PM) is characterized by rapid growth, local invasion, and limited therapeutic options. The multifunctional oncoprotein Y‐box‐binding protein‐1 (YB‐1) is frequently overexpressed in cancer and its inhibition reduces aggressive behavior in multiple tumor types. Here, we investigated the effects of YB‐1 on target gene regulation and PM cell behavior. Whereas siRNA‐mediated YB‐1 knockdown reduced cell motility, YB‐1 overexpression resulted in scattering, increased migration, and intravasation in vitro. Furthermore, YB‐1 stimulated PM cell spreading in zebrafish. Combined knockdown and inducible overexpression of YB‐1 allowed bidirectional control and rescue of cell migration, the pattern of which was closely followed by the mRNA and protein levels of EGFR and the protein level of snail, whereas the mRNA levels of MMP1, EPHA5, and PARK2 showed partial regulation by YB‐1. Finally, we identified snail as a critical regulator of YB‐1‐mediated cell motility in PM. This study provides insights into the mechanism underlying the aggressive nature of PM and highlights the important role of YB‐1 in this cancer. In this context, we found that YB‐1 closely regulates EGFR and snail, and, moreover, that YB‐1‐induced cell migration depends on snail. [ABSTRACT FROM AUTHOR]

Background: Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM tissue specimens compared with normal mesothelium. The objective of the current study was to further explore the role of FGF18 in PM and evaluate its suitability as a circulating biomarker. Methods: FGF18 mRNA expression was analyzed by real‐time PCR in cell lines and in silico in datasets from the Cancer Genome Atlas (TCGA). Cell lines overexpressing FGF18 were generated by retroviral transduction and cell behavior was investigated by clonogenic growth and transwell assays. Plasma was collected from 40 PM patients, six patients with pleural fibrosis, and 40 healthy controls. Circulating FGF18 was measured by ELISA and correlated to clinicopathological parameters. Results: FGF18 showed high mRNA expression in PM and PM‐derived cell lines. PM patients with high FGF18 mRNA expression showed a trend toward longer overall survival (OS) in the TCGA dataset. In PM cells with low endogenous FGF18 expression, forced overexpression of FGF18 resulted in reduced growth but increased migration. Surprisingly, despite the high FGF18 mRNA levels observed in PM, circulating FGF18 protein was significantly lower in PM patients and patients with pleural fibrosis than in healthy controls. No significant association of circulating FGF18 with OS or other disease parameters of PM patients was observed. Conclusions: FGF18 is not a prognostic biomarker in PM. Its role in PM tumor biology and the clinical significance of decreased plasma FGF18 in PM patients warrant further investigation. [ABSTRACT FROM AUTHOR]

We study the relaxation time of granular media in simple shear by means of DEM simulations (the methods being Molecular Dynamics as well as Contact Dynamics) in two and three dimensions with rough and with smooth frictional walls. While the system with rough walls behaves according to its steady state constitutive laws, the systems with smooth walls show a much stronger increase of the relaxation time with driving strength than to be expected. Employing a dynamic non-local rheology model[1] allows for a stronger increase but not sufficiently so.

In animals, stem cell populations of varying potency facilitate regeneration and tissue homeostasis. Notably, germline stem cells in both vertebrates and invertebrates express highly conserved RNA binding proteins, such as nanos , vasa , and piwi . In highly regenerative animals, these genes are also expressed in somatic stem cells, which led to the proposal that they had an ancestral role in all stem cells. In cnidarians, multi- and pluripotent interstitial stem cells have only been identified in hydrozoans. Therefore, it is currently unclear if cnidarian stem cell systems share a common evolutionary origin. We, therefore, aimed to characterize conserved stem cell marker genes in the sea anemone Nematostella vectensis . Through transgenic reporter genes and single-cell transcriptomics, we identify cell populations expressing the germline-associated markers piwi1 and nanos2 in the soma and germline, and gene knockout shows that Nanos2 is indispensable for germline formation. This suggests that nanos and piwi genes have a conserved role in somatic and germline stem cells in cnidarians.