Non-Small Cell Lung Carcinoma Cell Motility, Rac Activation and Metastatic Dissemination Are Mediated by Protein Kinase C Epsilon

Background: Protein kinase C (PKC) e, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCe in lung cancer metastasis has not yet been established. Principal Findings: Here we show that RNAi-mediated knockdown of PKCe in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCe depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCe with eV1-2, a specific PKCe inhibitor. PKCe was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCe-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis. Conclusions: Our results implicate PKCe as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target

Phaeobacter gallaeciensis genomes from globally opposite locations reveal high similarity of adaptation to surface life

Phaeobacter gallaeciensis, a member of the abundant marine Roseobacter clade, is known to be an effective colonizer of biotic and abiotic marine surfaces. Production of the antibiotic tropodithietic acid (TDA) makes P. gallaeciensis a strong antagonist of many bacteria, including fish and mollusc pathogens. In addition to TDA, several other secondary metabolites are produced, allowing the mutualistic bacterium to also act as an opportunistic pathogen. Here we provide the manually annotated genome sequences of the P. gallaeciensis strains DSM 17395 and 2.10, isolated at the Atlantic coast of north western Spain and near Sydney, Australia, respectively. Despite their isolation sites from the two different hemispheres, the genome comparison demonstrated a surprisingly high level of synteny (only 3% nucleotide dissimilarity and 88% and 93% shared genes). Minor differences in the genomes result from horizontal gene transfer and phage infection. Comparison of the P. gallaeciensis genomes with those of other roseobacters revealed unique genomic traits, including the production of iron-scavenging siderophores. Experiments supported the predicted capacity of both strains to grow on various algal osmolytes. Transposon mutagenesis was used to expand the current knowledge on the TDA biosynthesis pathway in strain DSM 17395. This first comparative genomic analysis of finished genomes of two closely related strains belonging to one species of the Roseobacter clade revealed features that provide competitive advantages and facilitate surface attachment and interaction with eukaryotic hosts

The Family Rhodobacteraceae

The family Rhodobacteraceae can be considered a paradigm of modern taxonomy of prokaryotes. Taking into account the number of species and genera that conforms the family, together with the knowledge about their abundance and vast global distribution, it surprises that most of them have been described relatively recent to our days. Two notable exceptions are Rhodonostoc capsulatum (Molisch, Die purpurbakterien nach neuen untersuchungen, vols i–vii. G. Fischer, Jena, pp 1–95, 1907) and Micrococcus denitrificans Beijerinck and Minkman (Zentbl Bakteriol, Parasitenkd, Infektionskr Hyg. Abt II 25:30–63, 1910), early basonyms of Rhodobacter capsulatus and Paracoccus denitrificans, respectively. The fact that so many descriptions within this family are recent means that some studies have been concomitant and pose a challenge not only for pure taxonomic studies but also for interpreting other studies in which a rapidly evolving nomenclature had to be used anyway. The metabolic and ecological diversity of the group adds further complexity. In spite of all these difficulties, the picture is far from being a chaos and it can be considered an exciting and important bacterial group to study. Rhodobacteraceae are, fundamentally, aquatic bacteria that frequently thrive in marine environments. They comprise mainly aerobic photo- and chemoheterotrophs but also purple non-sulfur bacteria which perform photosynthesis in anaerobic environments. They are deeply involved in sulfur and carbon biogeochemical cycling and symbiosis with aquatic micro- and macroorganisms. One hundred genera are currently recognized as members of the family although the Stappia group, Ahrensia, Agaricicola, and Rhodothalassium do not belong, phylogenetically, to the family. The 90 other genera are distributed in 5 phylogenetic groups (the Rhodobacter, the Paracoccus, the Rhodovulum, the Amaricoccus, and the Roseobacter clades) that might be considered a family on its own