INVESTIGATING THE INFLUENCE OF OXIDATIVE STRESS AND THE ROLE OF PRDX1 IN THE REGULATION OF LYSYL OXIDASE MEDIATED ECM AND COLLAGEN REMODELING IN BREAST CANCER METASTASIS

Breast cancer progression and metastasis includes not only cell-autonomous properties of cancer epithelial cells, but also the influence of the neighboring tumor stromal cells. In breast cancer, almost 80% of stromal associated fibroblasts (SAFs) acquire a cancer associated fibroblast (CAF)-like “activated phenotype”. This CAF activated phenotype is associated with elevated levels of reactive oxygen species (ROS) that are linked with tumor remodeling and spreading. Members of the lysyl oxidase (LOX) family of enzymes participate in tumor remodeling through the promotion of collagen crosslinking and collagen fibril production. We hypothesize that stromal Prdx1 regulates ROS dependent metastasis/migration of cancer cells through effects on LOX activity. Our preliminary data reveal that Prdx1 prevents CAF-induced malignant phenotypes in breast cancer (epithelial) cells in an H2O2-dependent manner. When compared to wild-type mice, Prdx1-/- SAFs show a marked increase in CAF-specific characteristics, including increased expression of CAF-specific markers, motility and invasiveness of SAFs and SAF-induced chemotactic migration and invasion by breast cancer epithelial cells in vitro. Lack of Prdx1 in mammary SAFs results in the upregulation of markers of the activated phenotype, such as collagen, vimentin and α-SMA leading to an increase in co-migration and invasion. As shPrdx1 SAFs show CAF-like mesenchymal properties in vitro, we tested in vivo if Prdx1 suppresses migration of breast cancer cells by generating a syngeneic mouse model to image BALB/c derived SAFs shPrdx1/SAFs pLKO1 (expressing iRFP). Immunoprecipitation data suggests that Prdx1 associates with LOX family proteins. Moreover, Prdx1-deficient SAFs displayed elevated LOX secretion into the ECM compared to Prdx1-proficient SAFs. Lastly, of translational relevance, we have shown that SAF Prdx1 becomes inactivated by cancer cells through phosphorylation of Y194 Prdx1. The peroxidase, Prdx1, is a regulator of LOX and CAF activity and SAFs lacking Prdx1 may serve as a valuable model system to investigate the biology of CAFs in vitro and in vivo

Signals Getting Crossed in the Entanglement of Redox and Phosphorylation Pathways: Phosphorylation of Peroxiredoxin Proteins Sparks Cell Signaling

Reactive oxygen and nitrogen species have cell signaling properties and are involved in a multitude of processes beyond redox homeostasis. The peroxiredoxin (Prdx) proteins are highly sensitive intracellular peroxidases that can coordinate cell signaling via direct reactive species scavenging or by acting as a redox sensor that enables control of binding partner activity. Oxidation of the peroxidatic cysteine residue of Prdx proteins are the classical post-translational modification that has been recognized to modulate downstream signaling cascades, but increasing evidence supports that dynamic changes to phosphorylation of Prdx proteins is also an important determinant in redox signaling. Phosphorylation of Prdx proteins affects three-dimensional structure and function to coordinate cell proliferation, wound healing, cell fate and lipid signaling. The advent of large proteomic datasets has shown that there are many opportunities to understand further how phosphorylation of Prdx proteins fit into intracellular signaling cascades in normal or malignant cells and that more research is necessary. This review summarizes the Prdx family of proteins and details how post-translational modification by kinases and phosphatases controls intracellular signaling

Signals Getting Crossed in the Entanglement of Redox and Phosphorylation Pathways: Phosphorylation of Peroxiredoxin Proteins Sparks Cell Signaling.

Reactive oxygen and nitrogen species have cell signaling properties and are involved in a multitude of processes beyond redox homeostasis. The peroxiredoxin (Prdx) proteins are highly sensitive intracellular peroxidases that can coordinate cell signaling via direct reactive species scavenging or by acting as a redox sensor that enables control of binding partner activity. Oxidation of the peroxidatic cysteine residue of Prdx proteins are the classical post-translational modification that has been recognized to modulate downstream signaling cascades, but increasing evidence supports that dynamic changes to phosphorylation of Prdx proteins is also an important determinant in redox signaling. Phosphorylation of Prdx proteins affects three-dimensional structure and function to coordinate cell proliferation, wound healing, cell fate and lipid signaling. The advent of large proteomic datasets has shown that there are many opportunities to understand further how phosphorylation of Prdx proteins fit into intracellular signaling cascades in normal or malignant cells and that more research is necessary. This review summarizes the Prdx family of proteins and details how post-translational modification by kinases and phosphatases controls intracellular signaling

Study of the aging of fermented of yacon (Smallanthus sonchifolius) and sensory profile and acceptance

Yacon is considered a functional food due to its the fructooligosaccharide (FOS) content, however its perishability and low production volume is a problem. The aim of this study was to analyze the changes in aging during one year of storage and conduct sensory analysis of fermented of yacon. For one year total acidity, volatile acidity, free and total sulfur dioxide, reducing sugars, sucrose, phenols and FOS and its antioxidant power were studied. At the end of aging a sensory profile and acceptance panel was performed. The total and volatile acidity increased significantly (p < 0.05). A decrease in fructooligosaccharide was also observed, indicating that yeasts are probably capable of hydrolyzing the latter. The total sulfur dioxide decreased significantly, demonstrating its ability to act well against oxidation products. This product showed good antioxidant capacity and sensory profiles of considerable acceptance. Therefore it can be affirmed that the alcoholic fermentation of yacon can be a good alternative for the industrial sector and farmers in the region could be encouraged to use large-scale production