Significance Nuclear envelope breakdown (NEB) leads to the exposure of nuclear structures to cytoplasmic activities. Greatwall is a kinase able to inhibit PP2A phosphatases that counteract Cdk-dependent phosphorylation required for mitosis. Here we show that Greatwall, an essential protein in mammals, is exported to the cytoplasm in a Cdk-dependent manner before NEB, thus protecting mitotic phosphates from phosphatase activity.

The alterations in carbohydrate metabolism that fuel tumor growth have been extensively studied. However, other metabolic pathways involved in malignant progression, demand further understanding. Here we describe a metabolic acyl-CoA synthetase/stearoyl-CoA desaturase ACSL/SCD network causing an epithelial-mesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells. The mesenchymal phenotype produced upon overexpression of these enzymes is reverted through reactivation of AMPK signaling. Furthermore, this network expression correlates with poorer clinical outcome of stage-II colon cancer patients. Finally, combined treatment with chemical inhibitors of ACSL/SCD selectively decreases cancer cell viability without reducing normal cells viability. Thus, ACSL/SCD network stimulates colon cancer progression through conferring increased energetic capacity and invasive and migratory properties to cancer cells, and might represent a new therapeutic opportunity for colon cancer treatment.

Bisphenol A (BPA), perfluorooctane sulfonate (PFOS), and tributyltin (TBT) are emerging endocrine disruptors (EDCs) with still poorly defined mechanisms of toxicity and metabolic effects in aquatic organisms. We used an untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic approach to study the effects of sub-lethal doses of these three EDCs on the metabolic profiles of zebrafish embryos exposed from 48 to 120hpf (hours post fertilization). Advanced chemometric data analysis methods were used to reveal effects on the subjacent regulatory pathways. EDC treatments induced changes in concentrations of about 50 metabolites for TBT and BPA, and of 25 metabolites for PFOS. The analysis of the corresponding metabolic changes suggested the presence of similar underlying zebrafish responses to BPA, TBT and PFOS affecting the metabolism of glycerophospholipids, amino acids, purines and 2-oxocarboxylic acids. We related the changes in glycerophospholipid metabolism to alterations in absorption of the yolk sack, the main source of nutrients (including lipids) for the developing embryo, linking the molecular markers with adverse phenotypic effects. We propose a general mode of action for all three chemical compounds, probably related to their already described interaction with the PPAR/RXR complex, combined with specific effects on different signaling pathways resulting in particular alterations in the zebrafish embryos metabolism.