The DEAD-box RNA helicase DDX28 suppresses cell migration and 3D growth and invasion in MDA-MB-231 cells by altering bioenergetics.

Hypoxia is a common characteristic of the tumor microenvironment leading to aggressive phenotypes. A major response to hypoxia is through the induction of gene programs by the hypoxia-inducible factors (HIF). Previously, we showed that the DEAD-box RNA helicase DDX28 negatively regulates hypoxic eIF4E2-directed translation through its interaction with HIF-2α.

Pharmacological inhibition of neuropeptide Y receptors Y1 and Y5 reduces hypoxic breast cancer migration, proliferation, and signaling.

Background: Neuropeptide Y (NPY) is an abundant neurohormone in human breast carcinomas that acts on a class of G-protein coupled receptors, of which NPY1R and NPY5R are the most highly expressed. This abundance is exploited for cancer imaging, but there is interest in pharmacological inhibition of the NPYRs to interrogate their functional relevance in breast cancer. We previously reported that NPY1R and NPY5R mRNA abundance is increased by hypoxia inducible factors, which sensitizes these receptors to NPY stimulation leading to enhanced migration and proliferation.

Spheroids as a 3D Model of the Hypoxic Tumor Microenvironment.

Spheroids enable the study of tumors and tumor hypoxia using a more representative model of the physiological environment compared to 2D cell culture. Spheroids can be grown in a cell suspension or when adhered to a solid scaffold. The spheroid formation method used is dependent on cell type.

Expression of hypoxia inducible factor-dependent neuropeptide Y receptors Y1 and Y5 sensitizes hypoxic cells to NPY stimulation.

Neuropeptide Y (NPY) is an abundant neurohormone in the central and peripheral nervous system involved in feeding behavior, energy balance, nociception, and anxiety. Several NPY receptor (NPYR) subtypes display elevated expression in many cancers including in breast tumors where it is exploited for imaging and diagnosis. Here, we address how hypoxia, a common feature of the tumor microenvironment, influences the expression of the NPYRs.

A novel allele of the Arabidopsis thaliana MACPF protein CAD1 results in deregulated immune signaling.

Immune recognition in plants is governed by two major classes of receptors: pattern recognition receptors (PRRs) and nucleotide-binding leucine-rich repeat receptors (NLRs). Located at the cell surface, PRRs bind extracellular ligands originating from microbes (indicative of "non-self") or damaged plant cells (indicative of "infected-self"), and trigger signaling cascades to protect against infection. Located intracellularly, NLRs sense pathogen-induced physiological changes and trigger localized cell death and systemic resistance.