BMP-6 promotes E-cadherin expression through repressing δEF1 in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Bone morphogenetic protein-6 (BMP-6) is critically involved in many developmental processes. Recent studies indicate that BMP-6 is closely related to tumor differentiation and metastasis.</p> <p>Methods</p> <p>Quantitative RT-PCR was used to determine the expression of BMP-6, E-cadherin, and δEF1 at the mRNA level in MCF-7 and MDA-MB-231 breast cancer cells, as well as in 16 breast cancer specimens. Immunoblot analysis was used to measure the expression of δEF1 at the protein level in δEF1-overexpressing and δEF1-interfered MDA-MB-231 cells. Luciferase assay was used to determine the rhBMP-6 or δEF1 driven transcriptional activity of the E-cadherin promoter in MDA-MB-231 cells. Quantitative CHIP assay was used to detect the direct association of δEF1 with the E-cadherin proximal promoter in MDA-MB-231 cells.</p> <p>Results</p> <p>MCF-7 breast cancer cells, an ER⁺cell line that expressed high levels of BMP-6 and E-cadherin exhibited very low levels of δEF1 transcript. In contrast, MDA-MB-231 cells, an ER^-cell line had significantly reduced BMP-6 and E-cadherin mRNA levels, suggesting an inverse correlation between BMP-6/E-cadherin and δEF1. To determine if the same relationship exists in human tumors, we examined tissue samples of breast cancer from human subjects. In 16 breast cancer specimens, the inverse correlation between BMP-6/E-cadherin and δEF1 was observed in both ER⁺cases (4 of 8 cases) and ER^-cases (7 of 8 cases). Further, we found that BMP-6 inhibited δEF1 transcription, resulting in an up-regulation of E-cadherin mRNA expression. This is consistent with our analysis of the E-cadherin promoter demonstrating that BMP-6 was a potent transcriptional activator. Interestingly, ectopic expression of δEF1 was able to block BMP-6-induced transactivation of E-cadherin, whereas RNA interference-mediated down-regulation of endogenous δEF1 in breast cancer cells abolished E-cadherin transactivation by BMP-6. In addition to down-regulating the expression of δEF1, BMP-6 also physically dislodged δEF1 from E-cadherin promoter to allow the activation of E-cadherin transcription.</p> <p>Conclusion</p> <p>We conclude that repression of δEF1 plays a key role in mediating BMP-6-induced transcriptional activation of E-cadherin in breast cancer cells. Consistent with the fact that higher level of δEF1 expression is associated with more invasive phenotype of breast cancer cells, our collective data suggests that δEF1 is likely the switch through which BMP-6 restores E-cadherin-mediated cell-to-cell adhesion and prevents breast cancer metastasis.</p

Analysis of the cohesion/adhesion proportion around bitumen-mineral failure interface under tensile loading

The occurrence of cohesive/adhesive hybrid failure at the bitumen-aggregate interface is widely acknowledged, however, the quantitative evaluation of the cohesion/adhesion proportion is relatively weak. This study explored cohesive/adhesive hybrid failure and provided a quantitative analysis of the proportion between cohesion and adhesion. For this reason, this study considered a variety of experimental factors that included temperature (5 °C, 15 °C, and 25 °C), mineral morphology (three mineral types and three surface textures), and measured film thickness (varying from 10 μm to 900 μm). By performing the bonding strength test, the strength was recorded and interface failure was accordingly captured. The results indicated that the cohesion/adhesion proportion varied significantly with the temperature, mineral morphology, and measured film thickness. In addition, it was found that bonding strength decreased with the increase in the film thickness and temperature, which can be well explained by variation in adhesion/cohesion proportion. Complete cohesive failure was observed when the film thickness increased beyond a critical value at a relatively high temperature. An additional noteworthy finding was the resemblance of a lunar crater for the failure interface at high temperatures, signifying the heterogeneous composition of the bituminous binder around the interface.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Pavement Engineerin

New generation artificial intelligence-driven intelligent manufacturing (NGAIIM)

Abstract In order to embrace new generation artificial intelligence to upgrade manufacturing industry, we propose the concept of new generation artificial intelligence-driven intelligent manufacturing (NGAIIM), which is a new manufacturing paradigm integrating human/machine/environment/information into product lifecycle activities. First, we introduce new generation artificial intelligence. Second, we present NGAIIM connotation, NGAIIM architecture and its technology system. Then, we examine a NGAIIM use case — CASICloud. Finally, we provide suggestions for directing the NGAIIM development