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Insulin resistance is accompanied by increased fasting glucagon and delayed glucagon suppression in individuals with normal and impaired glucose regulation

Hyperinsulinemia is an adaptive mechanism that enables the maintenance of normoglycemia in the presence of insulin resistance. We assessed whether glucagon is also involved in the adaptation to insulin resistance. A total of 1,437 individuals underwent an oral glucose tolerance test with measurements of circulating glucose, insulin, and glucagon concentrations at 0, 30 and 120 min. Early glucagon

STRIPAK components determine mode of cancer cell migration and metastasis

The contractile actomyosin cytoskeleton and its connection to the plasma membrane are critical for control of cell shape and migration. We identify three STRIPAK complex components, FAM40A, FAM40B and STRN3, as regulators of the actomyosin cortex. We show that FAM40A negatively regulates the MST3 and MST4 kinases, which promote the co-localization of the contractile actomyosin machinery with the E

The Different Roles of Aggrecan Interaction Domains

The aggregating proteoglycans of the lectican family are important components of extracellular matrices. Aggrecan is the most well studied of these and is central to cartilage biomechanical properties and skeletal development. Key to its biological function is the fixed charge of the many glycosaminoglycan chains, that provide the basis for the viscoelastic properties necessary for load distributi

Integrin β1, osmosensing, and chemoresistance in mouse ehrlich carcinoma cells

Background/Aims: Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β1, in cell volume regulation and drug-induced apoptosis in adherent and non-adherent Ehrlich ascites cell lines. M

The interaction between uPAR and vitronectin triggers ligand-independent adhesion signalling by integrins

The urokinase-type plasminogen activator receptor (uPAR) is a non-integrin vitronectin (VN) cell adhesion receptor linked to the plasma membrane by a glycolipid anchor. Through structure-function analyses of uPAR, VN and integrins, we document that uPAR-mediated cell adhesion to VN triggers a novel type of integrin signalling that is independent of integrin-matrix engagement. The signalling is ful

Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids

Protein kinase C iota (PKCι), a serine/threonine kinase required for cell polarity, proliferation and migration, is commonly up- or downregulated in cancer. PKCι is a human oncogene but whether this is related to its role in cell polarity and what repertoire of oncogenes acts in concert with PKCι is not known. We developed a panel of candidate oncogene expressing Madin-Darby canine kidney (MDCK) c

miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts

Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role

Arkadia regulates tumor metastasis by modulation of the TGF-β pathway

TGF-β can act as a tumor suppressor at early stages of cancer progression and as a tumor promoter at later stages. The E3 ubiquitin ligase Arkadia (RNF111) is a critical component of the TGF-β signaling pathway, being required for a subset of responses, those mediated by Smad3-Smad4 complexes. It acts by mediating ligand-induced degradation of Ski and SnoN (SKIL), which are 2 potent transcriptiona

Cancer dissemination--lessons from leukocytes

Cancer cells can move through tissues in a variety of different ways. In some cases, an epithelial-to-mesenchymal transition enables cancer cells to acquire fibroblast-like migratory properties. However, it is also becoming apparent that some cancer cells move in an amoeboid way similar to leukocytes. This theme will be the focus of the review, where we will discuss the similarities and difference

Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR

BACKGROUND: The urokinase receptor (uPAR/CD87) is highly expressed in malignant tumours. uPAR, as a GPI anchored protein, is preferentially located at the cell surface, where it interacts with its ligands urokinase (uPA) and the extracellular matrix protein vitronectin, thus promoting plasmin generation, cell-matrix interactions and intracellular signalling events. Interaction with a complex forme

The interaction between urokinase receptor and vitronectin in cell adhesion and signalling

The extracellular matrix (ECM) is a complex structural entity surrounding and supporting cells present in all tissue and organs. Cell-matrix interactions play fundamental roles during embryonic development, morphogenesis, tissue homoeostasis, wound healing, and tumourigenesis. Cell-matrix communication is kept in balance by physical contact and by transmembrane integrin receptors providing the dyn

Monomer dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies

To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer-oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein-uPAR in live cells, we analyzed the effect that e

uPAR-induced cell adhesion and migration : vitronectin provides the key

Expression of the membrane receptor uPAR induces profound changes in cell morphology and migration, and its expression correlates with the malignant phenotype of cancers. To identify the molecular interactions essential for uPAR function in these processes, we carried out a complete functional alanine scan of uPAR in HEK293 cells. Of the 255 mutant receptors characterized, 34 failed to induce chan

Limited inter- and intra-patient sequence diversity of the genetic lineage A human metapneumovirus fusion gene

Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein. In this study, the inter- and intra-patient genetic diversity of the lineage A hMPV F gene was investigated. T

Presence and significance of TT virus in Danish patients on maintenance hemodialysis

OBJECTIVES: To determine the prevalence of TT virus (TTV) in a population of Danish hemodialysis patients and evaluate possible relations between TTV infection and elevated levels of C-reactive protein (CRP) and hypo-response to treatment with erythropoietin (EPO).MATERIAL AND METHODS: Patients on maintenance hemodialysis at a single center were invited to participate. Demographic and clinical dat

TTV viral load as a marker for immune reconstitution after initiation of HAART in HIV-infected patients

PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART).METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples ta

Humour and Happiness in an NPM World : Do They Speak in Jest?

This study examines perceptions of humour and happiness in a world where NPM ideas have a profound influence on many aspects of everyday living. The researchers interviewed comedians and their circle of co-workers at comedy festivals. Comedians seek to make us laugh, but this paper examines whether they have a serious message, too. This research reveals comedians as critical thinkers, as edge-workThis study examines perceptions of humour and happiness in a world where NPM ideas have a profound influence on many aspects of everyday living. The researchers interviewed comedians and their circle of co-workers at comedy festivals. Comedians seek to make us laugh, but this paper examines whether they have a serious message, too. This research reveals comedians as critical thinkers, as edge-work