Fra-2 overexpression upregulates pro-metastatic cell-adhesion molecules, promotes pulmonary metastasis, and reduces survival in a spontaneous xenograft model of human breast cancer.

Purpose: The transcription factor Fra-2 affects the invasive potential of breast cancer cells by dysregulating adhesion molecules in vitro. Previous results suggested that it upregulates the expression of E- and P-selectin ligands. Such selectin ligands are important members of the leukocyte adhesion cascade, which govern the adhesion and transmigration of cancer cells into the stroma of the host organ of metastasis.

Xenograft-derived mRNA/miR and protein interaction networks of systemic dissemination in human prostate cancer.

Background: Distant metastasis formation is the major clinical problem in prostate cancer (PCa) and the underlying mechanisms remain poorly understood. Our aim was to identify novel molecules that functionally contribute to human PCa systemic dissemination based on unbiased approaches.

Methods: We compared mRNA, microRNA (miR) and protein expression levels in established human PCa xenograft tumours with high (PC-3), moderate (VCaP) or weak (DU-145) spontaneous micrometastatic potential.

Knockdown of L1CAM significantly reduces metastasis in a xenograft model of human melanoma: L1CAM is a potential target for anti-melanoma therapy.

Finding additional functional targets for combination therapy could improve the outcome for melanoma patients. In a spontaneous metastasis xenograft model of human melanoma a shRNA mediated knockdown of L1CAM more than sevenfold reduced the number of lung metastases after the induction of subcutaneous tumors for two human melanoma cell lines (MeWo, MV3). Whole genome expression arrays of the initially L1CAM high MeWo subcutaneous tumors revealed unchanged or downregulated genes involved in epithelial to mesenchymal transition (EMT) except an upregulation of Jagged 1, indicating a compensatory change in Notch signaling especially as Jagged 1 expression showed an increase in MeWo L1CAM metastases and Jagged 1 was expressed in metastases of the initially L1CAM low MV3 cells as well.

Comprehensive network of miRNA-induced intergenic interactions and a biological role of its core in cancer.

MicroRNAs (miRNAs) are a family of short noncoding RNAs that posttranscriptionally regulate gene expression and play an important role in multiple cellular processes. A significant percentage of miRNAs are intragenic, which is often functionally related to their host genes playing either antagonistic or synergistic roles. In this study, we constructed and analyzed the entire network of intergenic interactions induced by intragenic miRNAs.

Novel biomarkers in cancer: The whole is greater than the sum of its parts.

The major issues hampering progress in the treatment of cancer patients are distant metastases and drug resistance to chemotherapy. Metastasis formation is a very complex process, and looking at gene signatures alone is not enough to get deep insight into it. This paper reviews traditional and novel approaches to identify gene signature biomarkers and intratumoural fluid pressure both as a novel way of creating predictive markers and as an obstacle to cancer therapy.

Intracellular and extracellular microRNA: An update on localization and biological role.

MicroRNA (miRNA) is a class of small non-coding RNAs which mediate post-transcriptional gene silencing (PTGS) by sequence-specific inhibition of target mRNAs translation and/or lowering their half-lives in the cytoplasm. Together with their binding partners, Argonaute (AGO) proteins, miRNAs form cores of RNA-induced silencing complexes (RISC). Despite a substantial progress in understanding RISC structure, until recently little was known about its localization in the cell.

L1CAM: Cell adhesion and more.

L1CAM is a cell adhesion molecule of the immunoglobulin superfamily which was originally discovered as a major player in the development of the nervous system. L1CAM was demonstrated to have prognostic value in different cancers and to be a promising target for anti-cancer therapy. Here we overview the present data on L1CAM structure and function, regulation of its expression, role in cancer and therapeutic potential.

Modelling the metastatic cascade by in vitro microfluidic platforms.

The metastatic cascade comprises the following steps in sequential manner: the future metastatic cell has to leave the primary tumor mass, degrade the surrounding extracellular matrix, extravasate and circulate within in the bloodstream. Thereafter it has to attach to the endothelium of a target organ, intravasate into the connective tissue and has to proliferate to form a clinically detectable metastasis. We overview the in vitro microfluidic platforms modelling the metastatic cascade and the evolution towards systems capable of recapitulating all the steps by a single comprehensive model.

miRNome of inflammatory breast cancer.

Background: Inflammatory breast cancer (IBC) is an extremely malignant form of breast cancer which can be easily misdiagnosed. Conclusive prognostic IBC molecular biomarkers which are also providing the perspectives for targeted therapy are lacking so far. The aim of this study was to reveal the IBC-specific miRNA expression profile and to evaluate its association with clinicopathological parameters.

Importance of altered glycoprotein-bound N- and O-glycans for epithelial-to-mesenchymal transition and adhesion of cancer cells.

Aberrant glycosylation of cell surface glycoproteins acquired during malignant progression is a common characteristic of human cancer cells. Several biological processes and molecular mechanisms relevant for tumour progression are accompanied by altered mRNA expression levels of certain glycosyltransferases resulting in unusual ratios of common glycoconjugates present in a cancer cell's glycocalyx or even in the development of unusual, cancer-characterizing carbohydrates. This mini-review aims to give a concise overview on the current knowledge of the functional relevance of altered O- and N-glycans during two critical steps of tumour progression: (I) epithelial-to-mesenchymal transition of primary tumour cells during intravasation and (II) adhesion of circulating tumour cells towards the vascular wall during extravasation at a distant metastatic site.

Dynamically regulated miRNA-mRNA networks revealed by exercise.

Background: MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and the subsequent recovery period.

Results: Here we monitored the transcriptome changes using microarray analysis of the whole blood of eight highly trained athletes before and after 30 min of moderate exercise followed by 30 min and 60 min of recovery period.

Epithelial-mesenchymal transition: focus on metastatic cascade, alternative splicing, non-coding RNAs and modulating compounds.

Epithelial-mesenchymal transition (EMT) is a key process in embryonic development and metastases formation during malignant progression. This review focuses on transcriptional regulation, non-coding RNAs, alternative splicing events and cell adhesion molecules regulation during EMT. Additionally, we summarize the knowledge with regard to the small potentially druggable molecules capable of modulating EMT for cancer therapy.

Molecular architecture of zinc chelating small molecules that inhibit spliceosome assembly at an early stage.

The removal of intervening sequences (introns) from a primary RNA transcript is catalyzed by the spliceosome, a large ribonucleoprotein complex. At the start of each splicing cycle, the spliceosome assembles anew in a sequentially ordered manner on the pre-mRNA intron to be removed. We describe here the identification of a series of naphthalen-2-yl hydroxamate compounds that inhibit pre-mRNA splicing in vitro with mid- to high-micromolar values of IC(50).

2D format for screening bacterial cells at the throughput of flow cytometry.

We present a method for generating gel-based unordered 2D arrays of bacterial cells of a very high density, up to 10(5) cells per mm(2). Bacteria in a suspension are focused into a thin layer when the suspension and a dry gel matrix penetrate each other. Formation of a second gel from gel-forming components contained in the suspension results in immobilization of the cells.

HIS-24 linker histone and SIR-2.1 deacetylase induce H3K27me3 in the Caenorhabditis elegans germ line.

HIS-24 linker histone and SIR-2.1 deacetylase are involved in chromatin silencing in Caenorhabditis elegans. Depletion of SIR-2.

Expressible molecular colonies.

Carrying out polymerase chain reaction in a gel layer generates a 2-D pattern of DNA colonies comprising pure genetic clones. Here we demonstrate that transcription, translation and protein folding can be performed in the same gel. The resulting nucleoprotein colonies mimic living cells by serving as compartments in which the synthesized RNAs and proteins co-localize with their templates.

Molecular colony diagnostics: detection and quantitation of viral nucleic acids by in-gel PCR.

When PCR is carried out in a polyacrylamide gel, each target molecule forms a molecular colony that comprises many copies of the original template. By counting the number of colonies, one can directly determine the target titer, with 100% of the DNA molecules and approximately 15% of the RNA molecules being detected. Furthermore, because of the spatial separation of the products in the gel, no interference is observedfrom another simultaneously amplified target even if it is present at a 106 higher amount orfrom human nucleic acids that outweigh the target by up to a factor of 1,012, which is often true of clinical samples.