Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors.     

Molecular Mechanisms of the Deregulation of Muscle Contraction Induced by the R90P Mutation in Tpm3.12 and the Weakening of This Effect by BDM and W7

Point mutations in the genes encoding the skeletal muscle isoforms of tropomyosin can cause a range of muscle diseases. The amino acid substitution of Arg for Pro residue in the 90th position (R90P) in γ-tropomyosin (Tpm3.12) is associated with congenital fiber type disproportion and muscle weakness. The molecular mechanisms underlying muscle dysfunction in this disease remain unclear. Here, we observed that this mutation causes an abnormally high Ca²⁺-sensitivity of myofilaments in vitro and in muscle fibers. To determine the critical conformational changes that myosin, actin, and tropomyosin undergo during the ATPase cycle and the alterations in these changes caused by R90P replacement in Tpm3.12, we used polarized fluorimetry. It was shown that the R90P mutation inhibits the ability of tropomyosin to shift towards the outer domains of actin, which is accompanied by the almost complete depression of troponin’s ability to switch actin monomers off and to reduce the amount of the myosin heads weakly bound to F-actin at a low Ca²⁺. These changes in the behavior of tropomyosin and the troponin–tropomyosin complex, as well as in the balance of strongly and weakly bound myosin heads in the ATPase cycle may underlie the occurrence of both abnormally high Ca²⁺-sensitivity and muscle weakness. BDM, an inhibitor of myosin ATPase activity, and W7, a troponin C antagonist, restore the ability of tropomyosin for Ca²⁺-dependent movement and the ability of the troponin–tropomyosin complex to switch actin monomers off, demonstrating a weakening of the damaging effect of the R90P mutation on muscle contractility.     

Effect of Aluminum Content on the Dynamic Recrystallization of Fe18MnxAl0.74C Steels During Hot-Forging Treatments

Metallurgical and Materials Transactions A - In the present work, the dynamic recrystallization and microstructural evolution of the family of advanced high-strength steels Fe18MnxAl0.74C are...     

Mechanical and Corrosion Properties of ZrB2–SiC Composite Ceramics with Oxide Additions

Powder Metallurgy and Metal Ceramics - Hot pressing was used to produce compact ceramic samples with the following composition (wt.%): 60 ZrB2 + 20 SiC + 20 (Al2O3 + 32 t-ZrO2). The tetragonal...     

Viscosity of Conventional Cryolite-Alumina Melts

Russian Journal of Non-Ferrous Metals - Viscosity of conventional cryolite-alumina melts NaF–AlF3–CaF2–Al2O3 with a cryolite ratio (xNaF/xAlF3, mol/mol) 2.3 was studied in...     

Interaction of Components in Glass-Forming Melts of Iron and Nickel with Titanium,Zirconium, and Hafnium II. Temperature–Concentration Dependence of Thermodynamic Mixing Functions of Liquid Alloys

Powder Metallurgy and Metal Ceramics - The thermodynamic properties of liquid alloys in glass-forming systems were described in the framework of the associated solution model (ASM) according to the...     

Production of Steel 26KHMFBA Continuously-Cast Billets for Casing Pipes Using Barium-Containing Master Alloy

Metallurgist - Results are provided for a study showing the effect of Ca- and Ba-containing master alloys on composition and contamination with non-metallic inclusions during extra-furnace...     

Method for Controlling the Parameters and Characteristics of an Electric Arc to Evaluate the Efficiency of Using Briquetted Metallized Scale for Steel Smelting

Metallurgist - A method for controlling dynamic current-voltage characteristics in an electric arc furnace is described. The influence of the electrode’s current direct component on the...     

Reactions at the corroding nickel electrode in molten sodium carbonate under CO/CO2 atmosphere

Anodic reactions at the CO, CO₂|Ni electrode in molten sodium carbonate at 1000°C are examined in detail. Experimental polarization curves are fitted via a computer graphics procedure to a model employing five anodic reactions with activation, concentration and resistance polarization, and passivation. The resultant empirical parameters are interpreted in terms of absolute rate expressions describing possible anodic reactions. Three of the anodic reactions are found to be in accord with the findings at inert electrodes by previous investigators, i.e. oxidation of CO by two mechanisms and oxidation of carbonate, while the cathodic reaction is consistent with reduction of CO₂. The remaining two anodic reactions were associated with the oxidation of nickel to Ni²⁺ with formation of a NiO film above a passivation potential, and, at higher anodic overpotentials, oxidation of NiO to a higher oxide, e.g. Ni₂O₃. There is an indication of the formation of a third oxide at still higher anodic overpotentials.