Neutrophil extracellular traps (NETs) have been associated with several steps of tumor progression, including primary growth and metastasis. One of the key features for the acquisition of the metastatic ability is the epithelial–mesenchymal transition (EMT), a complex cellular program. In this study, we evaluated the ability of isolated NETs in modulating the pro-metastatic phenotype of human breast cancer cells. Tumor cells were treated with isolated NETs and then samples were generated for cell migration, quantitative RT-PCR, western blotting, immunofluorescence, and flow cytometry assays. RNA-seq data from The Cancer Genome Atlas (TCGA) database were assessed. NETs changed the typical epithelial morphology of MCF7 cells into a mesenchymal phenotype, a process that was accompanied by enhanced migratory properties. Additional EMT traits were observed: increased expression of N-cadherin and fibronectin, while the E-cadherin expression was repressed. Notably, NETs positively regulated the gene expression of several factors linked to the pro-inflammatory and pro-metastatic properties. Analyses of TCGA data showed that samples from breast cancer patients exhibit a significant correlation between pro-tumoral and neutrophil signature gene expression, including several EMT and pro-metastatic factors. Therefore, NETs drive pro-metastatic phenotype in human breast cancer cells through the activation of the EMT program.

BackgroundMosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source. However, the role of such molecules on mosquito vectorial capacity is unknown. Weather has been recognized as a major determinant of the spread of dengue, and plants under abiotic stress increase their production of polyphenols.ResultsHere, we show that including polyphenols in mosquito meals promoted the activation of AMP-dependent protein kinase (AMPK). AMPK positively regulated midgut autophagy leading to a decrease in bacterial proliferation and an increase in vector lifespan. Suppression of AMPK activity resulted in a 6-fold increase in midgut microbiota. Similarly, inhibition of polyphenol-induced autophagy induced an 8-fold increase in bacterial proliferation. Mosquitoes maintained on the polyphenol diet were readily infected by dengue virus.ConclusionThe present findings uncover a new direct route by which exacerbation of autophagy through activation of the AMPK pathway leads to a more efficient control of mosquito midgut microbiota and increases the average mosquito lifespan. Our results suggest for the first time that the polyphenol content and availability of the surrounding vegetation may increase the population of mosquitoes prone to infection with arboviruses.

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. EGFR may be activated by a diversity of mechanisms, including transactivation by G-protein coupled receptors (GPCRs). Studies have also shown that platelet-activating factor (PAF), a pro-inflammatory phospholipid mediator, plays an important role in the cancer progression either by modulating the cancer cells or the tumor microenvironment. Most of the PAF effects seem to be mediated by the interaction with its receptor (PAFR), a member of the GPCRs family. PAFR- and EGFR-evoked signaling pathways contribute to tumor biology; however, the interplay between them remains uninvestigated in cervical cancer. In this study, we employed The Cancer Genome Atlas (TCGA) and cancer cell lines to evaluate possible cooperation between EGFR, PAFR, and lysophosphatidylcholine acyltransferases (LPCATs), enzymes involved in the PAF biosynthesis, in the context of cervical cancer. It was observed a strong positive correlation between the expression of EGFR × PAFR and EGFR × LPCAT2 in 306 cervical cancer samples. The increased expression of LPCAT2 was significantly correlated with poor overall survival. Activation of EGFR upregulated the expression of PAFR and LPCAT2 in a MAPK-dependent fashion. At the same time, PAF showed the ability to transactivate EGFR leading to ERK/MAPK activation, cyclooxygenase-2 (COX-2) induction, and cell migration. The positive crosstalk between the PAF-PAFR axis and EGFR demonstrates a relevant linkage between inflammatory and growth factor signaling in cervical cancer cells. Finally, combined PAFR and EGFR targeting treatment impaired clonogenic capacity and viability of aggressive cervical cancer cells more strongly than each treatment separately. Collectively, we proposed that EGFR, LPCAT2, and PAFR emerge as novel targets for cervical cancer therapy.

Leishmania amazonensis is a species causative of cutaneous and anergic diffuse cutaneous leishmaniasis, treatment-resistant form, in the New World. Plants essential oils exhibit great potential as microbicide agents. We described the composition of the essential oils of two plants native from Brazil, Myrcia ovata, with geranial and neral as major constituents, and Eremanthus erythropappus, with α-bisabolol. In vitro effects of these essential oils on L. amazonensis promastigotes growth and ultrastructure were analysed as well as their cytotoxicity to murine macrophages. Both oils were highly active with IC 50 / 96 h of 8.69 and 9.53 µg/mL for M. ovata and E. erythropappus against promastigotes and caused ultrastructural alterations including mitochondrial enlargement. Cytotoxicity for murine macrophages varied with the oil concentrations. The IC 50 low values of both M. ovata and E. erythropappus oils against L. amazonensis and their relative low cytotoxicity to mammal host cells support their potential use against cutaneous leishmaniasis.