Netrins: Evolutionarily Conserved Regulators of Epithelial Fusion and Closure in Development and Wound Healing.

Epithelial remodelling plays a crucial role during development. The ability of epithelial sheets to temporarily lose their integrity as they fuse with other epithelial sheets underpins events such as the closure of the neural tube and palate. During fusion, epithelial cells undergo some degree of epithelial-mesenchymal transition (EMT), whereby cells from opposing sheets dissolve existing cell-cell junctions, degrade the basement membrane, extend motile processes to contact each other, and then re-establish cell-cell junctions as they fuse.

Maintenance of Cell Fate by the Polycomb Group Gene Sex Combs Extra Enables a Partial Epithelial Mesenchymal Transition in .

Epigenetic silencing by Polycomb group (PcG) complexes can promote epithelial-mesenchymal transition (EMT) and stemness and is associated with malignancy of solid cancers. Here we report a role for PcG repression in a partial EMT event that occurs during wing disc eversion, an early event during metamorphosis. In a screen for genes required for eversion we identified the PcG genes () and Depletion of or resulted in internalized wings and thoracic clefts, and loss of inhibited the EMT of the peripodial epithelium and basement membrane breakdown, ex vivo.

Photophysical and biological investigation of phenol substituted rhenium tetrazolato complexes.

The synthesis, structural and photophysical characterisation of four tricarbonyl rhenium(i) complexes bound to 1,10-phenanthroline and a tetrazolato ancillary ligand are reported. The complexes are differentiated by the nature (hydroxy or methoxy) and position (meta or para) of the substituent attached to the phenyl ring in conjugation to the tetrazole ring. The complexes exhibit phosphorescence emission from triplet charge transfer excited states, with the maxima around 600 nm, excited state lifetime decays in the 200-300 ns range, and quantum yield values of 4-6% in degassed acetonitrile solutions.

Loss of Neogenin1 in human colorectal carcinoma cells causes a partial EMT and wound-healing response.

Neogenin1 (NEO1) is a receptor of the Deleted in Colorectal Carcinoma (DCC)/Frazzled/UNC-40 family, which regulates axon guidance but can also stabilize epithelial adherens junctions. NEO1 and DCC are also tumor suppressors that can inhibit metastasis by acting as dependence receptors. Given the role of NEO1 in maintaining adherens junctions we tested whether loss of NEO1 also promoted metastasis via an epithelial mesenchymal transition (EMT).

Interaction Between Skeletal Muscle Cells and Extracellular Matrix Proteins Using a Serum Free Culture System.

The ability to grow C2C12 myoblasts in a completely defined, serum free medium enables researchers to investigate the role of specific factors in myoblast proliferation, migration, fusion, and differentiation without the confounding effects of serum. The use of defined, animal free in vitro culture systems will improve reproducibility between research groups and may also enhance translation of tissue engineering techniques into clinical applications. Here, we describe the use and characterization of a serum free culture system for C2C12 myoblasts using standard tissue culture medium and readily available, defined growth factors and supplements.

Frazzled can act through distinct molecular pathways in epithelial cells to regulate motility, apical constriction, and localisation of E-Cadherin.

Netrin receptors of the DCC/NEO/UNC-40/Frazzled family have well established roles in cell migration and axon guidance but can also regulate epithelial features such as adhesion, polarity and adherens junction (AJ) stability. Previously, we have shown that overexpression of Drosophila Frazzled (Fra) in the peripodial epithelium (PE) inhibits wing disc eversion and also generates cellular protrusions typical of motile cells. Here, we tested whether the molecular pathways by which Fra inhibits eversion are distinct from those driving motility.

A microRNA-7/growth arrest specific 6/TYRO3 axis regulates the growth and invasiveness of sorafenib-resistant cells in human hepatocellular carcinoma.

Unlabelled: Sorafenib remains the only approved drug for treating patients with advanced hepatocellular carcinoma (HCC). However, the therapeutic effect of sorafenib is transient, and patients invariably develop sorafenib resistance (SR). Recently, TYRO3, a member of the TYRO3-AXL-MER family of receptor tyrosine kinases, was identified as being aberrantly expressed in a significant proportion of HCC; however, its role in SR is unknown.

Silk fibroin scaffolds with muscle-like elasticity support in vitro differentiation of human skeletal muscle cells.

Human adult skeletal muscle has a limited ability to regenerate after injury and therapeutic options for volumetric muscle loss are few. Technologies to enhance regeneration of tissues generally rely upon bioscaffolds to mimic aspects of the tissue extracellular matrix (ECM). In the present study, silk fibroins from four Lepidoptera (silkworm) species engineered into three-dimensional scaffolds were examined for their ability to support the differentiation of primary human skeletal muscle myoblasts.

Interactions between Skeletal Muscle Myoblasts and their Extracellular Matrix Revealed by a Serum Free Culture System.

Decellularisation of skeletal muscle provides a system to study the interactions of myoblasts with muscle extracellular matrix (ECM). This study describes the efficient decellularisation of quadriceps muscle with the retention of matrix components and the use of this matrix for myoblast proliferation and differentiation under serum free culture conditions. Three decellularisation approaches were examined; the most effective was phospholipase A2 treatment, which removed cellular material while maximizing the retention of ECM components.

4-Hydroxy-trans-2-nonenal (4-HNE) induces neuronal SH-SY5Y cell death via hampering ATP binding at kinase domain of Akt1.

Inhibition mechanism(s) of protein kinase B/Akt1 and its consequences on related cell signaling were investigated in human neuroblastoma SH-SY5Y cells exposed to 4-hydroxy-trans-2-nonenal (4-HNE), one of the most reactive aldehyde by-products of lipid peroxidation. In silico data indicate that 4-HNE interacts with kinase domain of Akt1 with the total docking score of 6.0577 and also forms H-bond to Glu234 residue similar to highly potent Akt1 inhibitor imidazopiperidine analog 8b, in which the protonated imidazole nitrogen involves in two hydrogen bonds between Glu234 and Asp292.

Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells.

Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells.

Pharmacological inhibition of Hsp90 as a novel antitumor strategy to target cytoarchitecture through extracellular matrix signaling.

Pharmacological inhibition of Hsp90 in tumor cells induces anticancer effects through the destabilization of several oncogenic signaling molecules. Although there were reports that Hsp90 inhibition compromises cellular integrity, how this affects the cell adhesion through extracellular matrix (ECM) and integrin signaling is not known. Using human neuroblastoma (IMR-32), cervical (HeLa) and breast (MCF-7) cancer cells, and mouse embryonic carcinoma (PCC-4) cells, and using different substratum, glass, plastic, fibronectin, and matrigel, we demonstrate 17AAG induced alterations in integrin cross-linking with the actin cytoskeleton.