196 research outputs found

    CK1ε Is Required for Breast Cancers Dependent on β-Catenin Activity

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    Background: Aberrant β\beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate β\beta-catenin activity for therapeutic purposes have proven elusive to date. Methodology: To uncover genetic dependencies in breast cancer cells that harbor active β\beta-catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized β\beta-catenin activity. Here we identify CSNK1E, the gene encoding casein kinase 1 epsilon (CK1ε\varepsilon) as required specifically for the proliferation of breast cancer cells with activated β\beta-catenin and confirm its role as a positive regulator of β\beta-catenin-driven transcription. Furthermore, we demonstrate that breast cancer cells that harbor activated β\beta-catenin activity exhibit enhanced sensitivity to pharmacological blockade of Wnt/β\beta-catenin signaling. We also find that expression of CK1ε\varepsilon is able to promote oncogenic transformation of human cells in a β\beta-catenin-dependent manner. Conclusions/Significance: These studies identify CK1ε\varepsilon as a critical contributor to activated β\beta-catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active β\beta-catenin. More generally, these observations delineate an approach that can be used to identify druggable synthetic lethal interactions with signaling pathways that are frequently activated in cancer but are difficult to target with the currently available small molecule inhibitors

    'Barter', 'deals', 'bribes' and 'threats': Exploring Sibling Interactions

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    This paper investigates forms of strategic interaction between siblings during childhood. We argue that these interactions, characterised by notions of reciprocity, equivalence and constructions of fairness, are worked out in relation to responsibility, power, knowledge and sibling status. Birth order and age are not experienced as fixed hierarchies as they can be subverted, contested, resisted and negotiated. To explore these issues, in-depth individual and group interviews were conducted with a sample of 90 children between the ages of 5 and 17, drawn from 30 families of mixed socio-economic backgrounds in central Scotland with three siblings within this age range

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
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