ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases

Dry etching challenges for high- block copolymers

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Straightforward integration flow of a silicon containing block copolymer for line-space patterning

A promising alternative for the next-generation lithography is based on the directed self-assembly of block copolymers (BCPs) used as a bottom-up tool for the definition of nanometric features. Herein, a straightforward integration flow for line-space patterning is reported for a silicon BCP system, that is, poly­(1,1-dimethylsilacyclobutane)-<i>b</i>-poly­(styrene) (PDMSB-<i>b</i>-PS), able to define sub 15 nm features. Both in-plane cylindrical (<i>L</i>₀ = 20.7 nm) and out-of-plane lamellar structures (<i>L</i>₀ = 23.2 nm) formed through a rapid thermal annealing10 min at 180 °Cwere successfully integrated using graphoepitaxy to provide a long-range ordering of the BCP structure without the use of underlayers or top coats. Subsequent deep transfer into the silicon substrate using the hardened oxidized PDMSB domains as a mask is demonstrated. Combining a rapid self-assembly behavior, straightforward integration, and an excellent etching contrast, PDMSB-<i>b</i>-PS may become a material of choice for the next-generation lithography

Block-copolymers performances improvement and design for DSA applications in microelectronic

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Si-containing high- block-copolymers for nanolithography applications

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Materials meeting electronic requirements for Sub-10 nm lithography

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Interface optimization for high-chi block copolymers materials with sub-10 nm resolution

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Splitting kinetics of Si0.8_{0.8}Ge0.2_{0.2} layers implanted with H or sequentially with He and H

International audienceWe have performed systematic measurements of the splitting kinetics induced by H-only and He + H sequential ion implantation into relaxed Si$_{0.8}$Ge$_{0.2}$ layers and compared them with the data obtained in Si. For H-only implants, Si splits faster than Si$_{0.8}$Ge$_{0.2}$ Sequential ion implantation leads to faster splitting kinetics than H-only in both materials and is faster in Si$_{0.8}$Ge$_{0.2}$ than in Si. We have performed secondary ion mass spectrometry, Rutherford backscattering spectroscopy in channeling mode, and transmission electron microscopy analyses to elucidate the physical mechanisms involved in these splitting phenomena. The data are discussed in the framework of a simple phenomenological model in which vacancies play an important role

Scalability of advanced partially depleted n-MOSFET devices on biaxial strained SOI substrates

Biaxial tensile strained substrates offer strong electron mobility enhancements resulting in large drive current gains. For short channel n-MOSFETs, however, these improvements diminish. Root causes for this performance degradation are investigated through experiments and simulations. Elastic stress relaxation arising from shallow trench isolation (STI) is found to be negligible for current state-of-the-art transistors. On the other hand, parasitic source/drain resistance seems to be responsible for the limitation of drain current gains in deeply scaled devices. This effect is even further aggravated by an increased parasitic source/drain resistance in sSOI devices compared to standard SOI