Metastasis, responsible for most deaths from breast cancer (BC), is a multistep process leading to cancer cell spread. Extracellular matrix (ECM)-related adhesion and apoptosis resistance play pivotal role in metastasis. Ras suppressor-1 (RSU-1) localizes to cell-ECM adhesions and binds to pro-survival adhesion protein PINCH-1. Little is known about the role of RSU-1 in BC. In the present study, we investigated the role of RSU-1 in BC metastasis using two BC cell lines that differ in terms of their metastatic potential and a set of 32 human BC samples from patients with or without lymph node metastasis. We show that RSU-1 is upregulated in the aggressive MDA-MB-231 cells compared to MCF-7 and that its silencing by siRNA leads to upregulation of PINCH-1, induction of proliferation and reduction of apoptosis through downregulation of the pro-apoptotic gene p53-upregulated-modulator-of-apoptosis (PUMA). Our findings in the cell lines were further validated in the human BC tissues where normal adjacent tissues were used as controls. We demonstrate for the first time, that RSU-1 expression is upregulated in metastatic BC samples and downregulated in non-metastatic while it is negatively correlated with PINCH-1 and positively correlated with PUMA expression, suggesting that a pro-apoptotic mechanism is in place in metastatic BC samples and identifying RSU-1 as a potentially interesting molecule that needs to be evaluated further as a novel BC metastasis biomarker.

Our study provides novel evidence indicating that synergy between the leptin/Ob-Rb/STAT3 signalling pathway and the HER2 receptor protects tamoxifen-treated HER2 over-expressing cells from the inhibitory effect of tamoxifen through differential regulation of apoptosis-related genes.

Osteoarthritis (OA) is a debilitating disease of the joints characterized by cartilage degradation but to date there is no available pharmacological treatment to inhibit disease progression neither is there any available biomarker to predict its development. In the present study, we examined the expression level and possible involvement of novel cell-ECM adhesion-related molecules such as Iintegrin Linked Kinase (ILK), PINCH, parvin, Mig-2 and Migfilin in OA pathogenesis using primary human articular chondrocytes from healthy individuals and OA patients. Our findings show that only ILK and Migfilin were upregulated in OA compared to the normal chondrocytes. Interestingly, Migfilin silencing in OA chondrocytes rather exacerbated than ameliorated the osteoarthritic phenotype, as it resulted in even higher levels of catabolic and hypertrophic markers while at the same time induced reduction in ECM molecules such as aggrecan. Furthermore, we also provide a link between Migfilin and β-catenin activation in OA chondrocytes, showing Migfilin to be inversely correlated with β-catenin. Thus, the present study emphasizes for the first time to our knowledge the role of Migfilin in OA and highlights the importance of cell-ECM adhesion proteins in OA pathogenesis.

Targeted virome enrichment and sequencing (VirCapSeq-VERT) utilizes a pool of oligos (baits) to enrich all known—up to 2015—vertebrate-infecting viruses, increasing their detection sensitivity. The hybridisation of the baits to the target sequences can be partial, thus enabling the detection and genomic reconstruction of novel pathogens with <40% genetic diversity compared to the strains used for the baits’ design. In this study, we deploy this method in multiplexed mixes of viral extracts, and we assess its performance in the unbiased detection of DNA and RNA viruses after cDNA synthesis. We further assess its efficiency in depleting various background genomic material. Finally, as a proof-of-concept, we explore the potential usage of the method for the characterization of unknown, emerging human viruses, such as SARS-CoV-2, which may not be included in the baits’ panel. We mixed positive samples of equimolar DNA/RNA viral extracts from SARS-CoV-2, coronavirus OC43, cytomegalovirus, influenza A virus H3N2, parvovirus B19, respiratory syncytial virus, adenovirus C and coxsackievirus A16. Targeted virome enrichment was performed on a dsDNA mix, followed by sequencing on the NextSeq500 (Illumina) and the portable MinION sequencer, to evaluate its usability as a point-of-care (PoC) application. Genome mapping assembly was performed using viral reference sequences. The untargeted libraries contained less than 1% of total reads mapped on most viral genomes, while RNA viruses remained undetected. In the targeted libraries, the percentage of viral-mapped reads were substantially increased, allowing full genome assembly in most cases. Targeted virome sequencing can enrich a broad range of viruses, potentially enabling the discovery of emerging viruses.