Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3

International audienceABSTRACT: BACKGROUND: Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to endothelial cells. It requires interactions between adhesion receptors on endothelial cells and their counter-receptors on cancer cells. Notably, E-selectin, a major endothelial adhesion receptor, interacts with Death receptor-3 present on metastatic colon carcinoma cells. This interaction confers metastatic properties to colon cancer cells by promoting the adhesion of cancer cells to endothelial cells and triggering the activation of the pro-migratory p38 and pro-survival ERK pathways in the cancer cells. In the present study, we investigated further the mechanisms by which the E-selectin-activated pathways downstream of DR3 confer a survival advantage to colon cancer cells. METHODS: Cell survival has been ascertained by using the WST-1 assay and by evaluating the activation of the PI3 kinase/NFκB survival axis. Apoptosis has been assayed by determining DNA fragmentation by Hoechst staining and by measuring cleavage of caspases-8 and -3. DR3 isoforms have been identified by PCR. For more precise quantification, targeted PCR reactions were carried out, and the amplified products were analyzed by automated chip-based microcapillary electrophoresis on an Agilent 2100 Bioanalyzer instrument. RESULTS: Interaction between DR3-expressing HT29 colon carcinoma cells and E-selectin induces the activation of the PI3K/Akt pathway. Moreover, p65/RelA, the anti-apoptotic subunit of NFκB, is rapidly translocated to the nucleus in response to E-selectin. This translocation is impaired by the PI3K inhibitor LY294002. Furthermore, inhibition of the PI3K/Akt pathway increases the cleavage of caspase 8 in colon cancer cells treated with E-selectin and this effect is still further increased when both ERK and PI3K pathways are concomitantly inhibited. Intriguingly, metastatic colon cancer cell lines such as HT29 and SW620 express higher levels of a splice variant of DR3 that has no trans-membrane domain and no death domain. CONCLUSION: Colon cancer cells acquire an increased capacity to survive via the activation of the PI3K/NFκB pathway following the stimulation of DR3 by E-selectin. Generation of a DR3 splice variant devoid of death domain can further contribute to protect against apoptosis

European Red List of Habitats Part 1. Marine habitats

The European Red List of Habitats provides an overview of the risk of collapse (degree of endangerment) of marine, terrestrial and freshwater habitats in the European Union (EU28) and adjacent regions (EU28+), based on a consistent set of categories and criteria, and detailed data and expert knowledge from involved countries1. A total of 257 benthic marine habitat types were assessed. In total, 19% (EU28) and 18% (EU28+) of the evaluated habitats were assessed as threatened in categories Critically Endangered, Endangered and Vulnerable. An additional 12% were Near Threatened in the EU28 and 11% in the EU28+. These figures are approximately doubled if Data Deficient habitats are excluded. The percentage of threatened habitat types differs across the regional seas. The highest proportion of threatened habitats in the EU28 was found in the Mediterranean Sea (32%), followed by the North-East Atlantic (23%), the Black Sea (13%) and then the Baltic Sea (8%). There was a similar pattern in the EU28+. The most frequently cited pressures and threats were similar across the four regional seas: pollution (eutrophication), biological resource use other than agriculture or forestry (mainly fishing but also aquaculture), natural system modifications (e.g. dredging and sea defence works), urbanisation and climate change. Even for habitats where the assessment outcome was Data Deficient, the Red List assessment process has resulted in the compilation of a substantial body of useful information to support the conservation of marine habitats

Role of genetic polymorphisms in tumour angiogenesis

Angiogenesis plays a crucial role in the development, growth and spread of solid tumours. Pro- and anti-angiogenic factors are abnormally expressed in tumours, influencing tumour angiogenesis, growth and progression. Polymorphisms in genes encoding angiogenic factors or their receptors may alter protein expression and/or activity. This article reviews the literature to determine the possible role of angiogenesis-related polymorphisms in cancer. Further research studies in this potentially crucial area of tumour biology are proposed

Usage of ferromagnetic devices in the diagnostic activities regarding the buildings

W dobie dzisiejszych czasów konstruktorzy stają coraz częściej przed wyzwaniem zaprojektowania nadbudowy lub adaptacji istniejących budowli pod nowe obciążenia. Konieczne jest tym celu stosunkowo szybkie i ekonomiczne rozwiązanie w rozpoznaniu wszystkich elementów konstrukcji. W przypadku rozpoznania liczby i rozkładu prętów zbrojeniowych przydatne wydają się dostępne na rynku urządzenia ferromagnetyczne znane powszechnie pod nazwą skanery zbrojenia.In recent times, the designers, more and more often, face the challenge of designing an additional part of the building or a challenge of adapting the building in a way that would make it possible for its structure to withstand the newly imposed loads. In order to face the above challenges, it is required to create solutions, quickly and economically, which would make it possible to recognize the structure in case of all of the construction elements. In case when a need arises to find out the number and the distribution of the reinforcing bars, ferromagnetic devices, which are commonly known as reinforcement scanners, are particularly usable

Strength parameters of subfloors specified using various methods

Podkłady podłogowe są bezpośrednim podłożem pod posadzką. Od parametrów wytrzymałościowych podkładów zależy, jaki rodzaj podłogi możemy wykonać oraz jaką trwałością będzie się ona charakteryzować. W przypadku nowo wznoszonych budynków i wykonywania nowych podkładów możemy na bieżąco kontrolować jakość wykonywanych podkładów w oparciu o obowiązujące normy. W przypadku oceny parametrów wytrzymałościowych istniejących już podkładów brak jest kryteriów oceny oraz metodyki badań. W niniejszym artykule na podstawie badań porównawczych określono zależności nie ujęte w normach.Subfloors constitute a direct ground under the flooring. Strength parameters of subfloors determine the type of floor that can be created as well as its durability. In the case of newly erected buildings and creation of new subfloors, it is possible to systematically control the quality of created subfloors based on existing norms. In the case of evaluation of strength parameters of already existing subfloors, no evaluation criteria have been specified and there is no test methodology available. On the basis of comparative tests, the article discusses the relations which are not presented in the norms