Regulation of cell migration in cancer: investigation into the regulation of cancer cell blebbing in the extracellular matrix

Cell migration is a highly coordinated process and any aberration in the regulatory mechanisms could result in pathological conditions such as cancer. The ability of cancer cells to disseminate to distant sites within the body has made it difficult to treat. Cancer cells also exhibit plasticity that makes them able to interconvert from an elongated, mesenchymal morphology to an amoeboid blebbing form under different physiological conditions. Blebs are spherical membrane protrusions formed by actomyosin-mediated contractility of cortical actin resulting in increased hydrostatic pressure and subsequent detachment of the membrane from the cortex. Tumour cells use blebbing as an alternative mode of migration by squeezing through preexisting gaps in the ECM, and bleb formation is believed to be mediated by the Rho-ROCK signaling pathway. However, the involvement of transmembrane water and ion channels in cell blebbing has not been examined. In the present study, the role of the transmembrane water channels, aquaporins, transmembrane ion transporters and lipid signaling enzymes in the regulation of blebbing was investigated. Using 3D matrigel matrix as an in vitro model to mimic normal extracellular matrix, and a combination of confocal and time-lapse microscopy, it was found that AQP1 knockdown by siRNA ablated blebbing of HT1080 and ACHN cells, and overexpression of AQP1-GFP not only significantly increased bleb size with a corresponding decrease in bleb numbers, but also induced bleb formation in non-blebbing cell lines. Importantly, AQP1 overexpression reduces bleb lifespan due to faster bleb retraction. This novel finding of AQP1-facilitated bleb retraction requires the activity of the Na+/H+ pump as inhibition of the ion transporter, which was found localized to intracellular vesicles, blocked bleb retraction in both cell lines. This study also demonstrated that a differential regulation of cell blebbing by AQP isoforms exists as knockdown of AQP5 had no effect on bleb formation. Data from this study also demonstrates that the lipid signaling PLD2 signals through PA in the LPA-LPAR-Rho-ROCK axis to positively regulate bleb formation in both cell lines. Taken together, this work provides a novel role of AQP1 and Na+/H+ pump in regulation of cell blebbing, and this could be exploited in the development of new therapy to treat cancer.

Contrastive analysis of keywords in discourses: intégration and integration in French and German discourses about migration

This article suggests a theoretical and methodological framework for a systematic contrastive discourse analysis across languages and discourse communities through keywords, constituting a lexical approach to discourse analysis which is considered to be particularly fruitful for comparative analysis. We use a corpus assisted methodology, presuming meaning to be constituted, revealed and constrained by collocation environment. We compare the use of the keyword intégration and Integration in French and German public discourses about migration on the basis of newspaper corpora built from two French and German newspapers from 1998 to 2011. We look at the frequency of these keywords over the given time span, group collocates into thematic categories and discuss indicators of discursive salience by comparing the development of collocation profiles over time in both corpora as well as the occurrence of neologisms and compounds based on intégration/Integration.

Effect of aluminium on migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells in culture

Aluminium (Al) has been measured in human breast tissue, and may be a contributory factor in breast cancer development. At the 10th Keele meeting, we reported that long-term exposure to Al could increase migratory properties of oestrogen-responsive MCF-7 human breast cancer cells suggesting a role for Al in the metastatic process. We now report that long-term exposure (20–25 weeks) to Al chloride or Al chlorohydrate at 10−4 M or 10−5Mconcentrations can also increase themigration of oestrogen unresponsiveMDA-MB-231 human breast cancer cells as measured using time-lapse microscopy and xCELLigence technology. In parallel, Al exposure was found to give rise to increased secretion of active matrixmetalloproteinaseMMP9 as measured by zymography, and increased intracellular levels of activated MMP14 as measured by western immunoblotting. These results demonstrate that Al can increase migration of human breast cancer cells irrespective of their oestrogen responsiveness, and implicate alterations to MMPs as a potential mechanism worthy of further study.

Recovering the counterfactual wage distribution with selective return migration

This paper recovers the distribution of wages for Mexican-born workers living in the U.S. if no return migration of Mexican-born workers occurred. Because migrants self-select in the decision to return, the overarching problem addressed by this study is the use of an estimator that also accounts for selection on unobservables. I find that Mexican returnees are middle- to high-wage earners at all levels of educational attainment. Taking into account self-selection in return migration, wages would be approximately 7.7% higher at the median and 4.5% higher at the mean. Owing to positive self-selection, the immigrant-native wage gap would, therefore, partially close if there was no return migration.

Genomic signals of migration and continuity in Britain before the Anglo-Saxons

The purported migrations that have formed the peoples of Britain have been the focus of generations of scholarly controversy. However, this has not benefited from direct analyses of ancient genomes. Here we report nine ancient genomes (~1 x) of individuals from northern Britain: seven from a Roman era York cemetery, bookended by earlier Iron-Age and later Anglo-Saxon burials. Six of the Roman genomes show affinity with modern British Celtic populations, particularly Welsh, but significantly diverge from populations from Yorkshire and other eastern English samples. They also show similarity with the earlier Iron-Age genome, suggesting population continuity, but differ from the later Anglo-Saxon genome. This pattern concords with profound impact of migrations in the Anglo-Saxon period. Strikingly, one Roman skeleton shows a clear signal of exogenous origin, with affinities pointing towards the Middle East, confirming the cosmopolitan character of the Empire, even at its northernmost fringes.

Talent on the move: creative human capital migration patterns in UK

The last decade has seen an increasing number of contributions, from both academics and policy makers, focusing on the role of higher education in developing human capital (Charles, 2003; Cramphorn & Woodlhouse, 1999; Preston & Hammond, 2006) and hence contributing to local and regional growth (Faggian & McCann, 2006; Mathur, 1999; Moretti, 2004). Within this broader literature, the role played by more ‘scientific’ types of human capital, such as STEM (science, technology, engineering, and mathematics) graduates and science parks (Bozeman, Dietz, & Gaughan, 2001; Linderlöf & Löfsten, 2004; Löfsten & Lindelöf, 2005), has also been explored. Little attention has been paid so far, to the role played by more ‘creative’ types of human capital. This chapter aims at filling this gap, in light of the central role that the term ‘creative’ took in policy and academic discourses in the UK (Comunian & Faggian, 2011; Comunian & Gilmore, 2015; DCMS, 2006; Powell, 2007; Universities UK, 2010).