Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation

NHERF1/EBP50 (Na+/H+ exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells. This movement depended on direct binding of NHERF1 to C-terminally phosphorylated ERM proteins (cpERMs). Moreover, NHERF1 depletion downregulated cpERMs and further impaired cpERM-dependent remodeling of the cell cortex, suggesting reciprocal regulation between these proteins. The LPA-induced protein complex was highly enriched in migratory pseudopodia, whose formation was impaired by overexpression of NHERF1 truncation mutants. Consistent with this, NHERF1 depletion in various types of cancer cells abolished chemotactic cell migration toward a LPA gradient. Taken together, our findings suggest that the high dynamics of cytosolic NHERF1 provide cancer cells with a means of controlling chemotactic migration. This capacity is likely to be essential for ovarian cancer progression in tumor microenvironments containing LPA

Storage of Nuclear Excitation Energy through Magnetic Switching

The decay rate of 57Fe nuclei in an 57FeBO3 crystal excited by 14.4 keV synchrotron radiation pulses was controlled by switching the direction of the crystal magnetization. Abrupt switching some nanoseconds after excitation suppresses the coherent nuclear decay. Switching back at later times restores it, starting with an intense radiation spike. The enhanced delayed reemission is due to the release of the energy stored during the period of suppression. Suppression and restoration originate from drastic changes of the nuclear states and of the interference within the nuclear transitions

Solarkampagne 'Solar - na klar.' Abschlussbericht

The German market for technically matured solar-thermal systems for generating hot water is growing by 20 per cent per year, with some deviations due to incentive policies. This growth can be and is planned to be increased systematically, with following goals: A practical contribution to the Federal Government's efforts to achieve the goals regarding the protection of climate; creating future-oriented jobs; supporting ecologically sustainable ways of life and models of consumption by convincing the consumers and other target groups of the fact that it makes sense already today to start utilizing solar energy and to invest also on private basis. These targets are expected to be set up with the help of a three-year mass campaign (1999 until 2001), i.e. the campaign called ''Solar - na klar.'' (solar - of course).Der deutsche Markt fuer die technisch ausgereiften solarthermischen Anlagen zur Warmwassererzeugung waechst mit ca. 20% p.a., mit foerderpolitisch bedingten Schwankungen. Dieses Wachstum kann und soll systematisch gesteigert werden, mit folgenden Zielsetzungen: Praktischer Beitrag zur Erreichung der Klimaschutzziele der Bundesregierung; Schaffung zukunftsorientierter Arbeitsplaetze; Befoerderung oekologisch nachhaltiger Lebensstile und Konsummuster durch die Ueberzeugung der Verbraucher und weiterer Zielgruppen, dass es heute bereits sinnvoll ist, in die Nutzung der Solarenergie konkret einzusteigen und auch privat zu investieren. Diese Ziele sollen mithilfe einer auf drei Jahre angelegten Breitenkampagne (1999 bis 2001), d.h. der Kampagne 'Solar - na klar.' erfolgen. (orig.)Available from TIB Hannover: F02B486 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDeutsche Bundesstiftung Umwelt, Osnabrueck (Germany)DEGerman

Assessment of CXC ligand 12-mediated calcium signalling and its regulators in basal-like breast cancer cells

CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Casignalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Caresponses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells. Cluster of differentiation (CD)24, the negative regulator of CXCL12 responses, demonstrated increased expression in MDA-MB-468 cells compared with MDA-MB-231 cells, and the two cell lines expressed comparable levels of hypoxia-inducible factor (HIF)2α, a CXCR4 regulator. Induction of epithelial-mesenchymal transition (EMT) by epidermal growth factor exhibited opposite effects on CXCR4 mRNA levels compared with hypoxia-induced EMT. Neither EMT inducer exhibited an effect on CXCR7 expression, however hypoxia increased HIF2α expression levels in MDA-MB-468 cells. Analysis of the gene expression profiles of breast tumours revealed that the highest expression levels of CXCR4 and CXCR7 were in the Claudin-Low molecular subtype, which is markedly associated with EMT features