Heat-shock protein 90α protects NME1 against degradation and suppresses metastasis of breast cancer.

BACKGROUND: NME1 has been exploited as a potential translational target for decades. Substantial efforts have been made to upregulate the expression of NME1 and restore its anti-metastasis function in metastatic cancer. METHODS: Cycloheximide (CHX) chase assay was used to measure the steady-state protein stability of NME1 and HSP90α. The NME1-associating proteins were identified by immunoprecipitation combined with mass spectrometric analysis. Gene knockdown and overexpression were employed to examine the impact of HSP90AA1 on intracellular NME1 degradation. The motility and invasiveness of breast cancer cells were examined in vitro using wound healing and transwell invasion assays. The orthotopic spontaneous metastasis and intra-venous experimental metastasis assays were used to test the formation of metastasis in vivo, respectively. RESULTS: HSP90α interacts with NME1 and increases NME1 lifetime by impeding its ubiquitin-proteasome-mediated degradation. HSP90α overexpression significantly inhibits the metastatic potential of breast cancer cells in vitro and in vivo. A novel cell-permeable peptide, OPT22 successfully mimics the HSP90α function and prolongs the life span of endogenous NME1, resulting in reduced metastasis of breast cancer. CONCLUSION: These results not only reveal a new mechanism of NME1 degradation but also pave the way for the development of new and effective approaches to metastatic cancer therapy.

The SET oncoprotein promotes estrogen-induced transcription by facilitating establishment of active chromatin.

SET is a multifunctional histone-binding oncoprotein that regulates transcription by an unclear mechanism. Here we show that SET enhances estrogen-dependent transcription. SET knockdown abrogates transcription of estrogen-responsive genes and their enhancer RNAs. In response to 17ß-estradiol (E2), SET binds to the estrogen receptor α (ERα) and is recruited to ERα-bound enhancers and promoters at estrogen response elements (EREs). SET functions as a histone H2 chaperone that dynamically associates with H2A.Z via its acidic C-terminal domain and promotes H2A.Z incorporation, ERα, MLL1, and KDM3A loading and modulates histone methylation at EREs. SET depletion diminishes recruitment of condensin complexes to EREs and impairs E2-dependent enhancer-promoter looping. Thus, SET boosts E2-induced gene expression by establishing an active chromatin structure at ERα-bound enhancers and promoters, which is essential for transcriptional activation.

Oncoprotein SET dynamically regulates cellular stress response through nucleocytoplasmic transport in breast cancer.

SETß is the predominant isoform of oncoprotein SE translocation (SET) in various breast cancer cell lines. Interactome-transcriptome analysis has shown that SETß is intimately associated with cellular stress response. Among various exogenous stimuli, formaldehyde (FA) causes distinct biological effects in a dose-dependent manner. In response to FA at different concentrations, SET dynamically shuttles between the nucleus and cytoplasm, performing diverse biofunctions to restore homeostasis. At a low concentration, FA acts as an epidermal growth factor (EGF) and activates the HER2 receptor and downstream signaling pathways in HER2+ breast cancer cells, resulting in enhanced cell proliferation. Nucleocytoplasmic transport of SETß is controlled by the PI3K/PKCα/CK2α axis and depletion or blockade of the transport of SETß suppresses EGF-induced activation of AKT and ERK. SETß also inhibits not only stress-induced activation of p38 MAPK signaling pathway, but also assembly of stress granules by hindering formation of the G3BP1-RNA complex. Our findings suggest that SET functions as an important regulator which modulates cellular stress signaling pathways dynamically.

SET/PP2A signaling regulates macrophage positioning in hypoxic tumor regions by amplifying chemotactic responses.

Tumor-associated macrophages (TAMs) are one of the main cellular components in the tumor microenvironment (TME). In many types of solid tumors, TAMs tend to accumulate in hypoxic areas and are intimately related to poor patient prognosis. However, the underlying mechanisms by which TAMs infiltrate hypoxic tumor regions remain unclear. In this study, we report that genetic deletion of SE translocation (SET) in myeloid cells inhibited the entry of TAMs into the hypoxic tumor region and abated their proangiogenic and immunosuppressive functions, ultimately inhibiting tumor growth. Mechanistically, in response to hypoxic tumor supernatant stimulation, SET in macrophages shuttled between the nucleus and cytoplasm via the PKC-CK2α signaling axis. Cytoplasmic retention of SET increased ERK and P38 signaling by inhibiting PP2A, which promoted TAM migration into the hypoxic area and polarization toward the M2 phenotype. Therefore, we conclude that SET modulates tumor immunity by acting as a key regulator of macrophage positioning and function in the tumor.

Dynamics of estrogen-induced ROS and DNA strand break generation in estrogen receptor α-positive breast cancer.

DNA repair machinery is involved in estrogen-dependent transactivation. Mounting evidence suggests that mechanisms underlying estrogen-induced DNA damage are complicated. To date estrogen-induced DNA oxidation and its impact on ERα-mediated transaction remains ambiguous. Herein, we found that the process of 17ß-estradiol (E2)-induced ROS production can be approximately divided into two phases according to responding time and generation mechanisms. The intracellular Ca2+ fluctuation and ERα-dependent transcription lead to temporospatially different oxidative DNA damage. Further, we demonstrate that DNA oxidation is dispensable for estrogen-responsive gene expression. Dynamics of estrogen-induced DNA strand break generation also show two-phase pattern and topoisomerase-mediated DNA stand breaks are essential in estrogen signaling. Collectively, our findings have provided new insights into oxidative DNA damage in estrogen signaling.

Leveraging Hydrophilic Hierarchical Channels to Regulate Excessive Water for High-Efficiency Solar Steam Yield.

Both the solar absorptance and water content in solar-driven interface evaporation (SDIE) devices are of equal importance for efficient solar steam yield and freshwater production, but water content regulation has garnered relatively less attention, as it is more challenging to balance the water supply rate and the evaporation rate inside SDIE devices. Herein, an SDIE device is designed by coating natural luffa with polypyrrole, which could effectively regulate the water content during the solar steam yield by its unique hydrophilic hierarchical channels to transform excessive water from the bulk state into the film state on the porous skeleton. The hierarchical channels revealed by cryoelectron microscopy experiments not only reduce the loss of heat in unevaporated water but also offer abundant escape channels for solar steam, thus enabling the proposed SDIE device to achieve an evaporation rate of 2.38 kg m-2 h-1 under 1 sun illumination. This work reveals the key role of hierarchical channels for water regulation in the high-efficiency solar steam yield and triggers further application of natural biomaterials with unique structures in the field of solar interfacial evaporation.

Efficient Removal of Dye from Wastewater without Selectivity Using Activated Carbon-Juncus effusus Porous Fibril Composites.

Adsorption techniques have been successfully applied in water purification because of their flexibility, simplicity of design, and effectiveness. Activated carbon is an effective absorbent using for dye adsorption; however, the powder structure is not conducive for practical applications and cannot be used to filter dye solutions which are challenges that still need to be addressed. Herein, a natural cellulose-based absorbent, activated carbon-Juncus effusus fiber (AC-JE fiber), demonstrates the removal of all kinds of dyes without selectivity and humic substances and humic-like organics from wastewater. The combined macroporous structures of JE fibers and the microporous and mesoporous structures of activated carbon particles enhance their adsorption properties. These composite absorbents have excellent adsorption and continuous filtration effect. The rejection rate is approximately 100% not only on acidic and anionic dyes but also on basic and cationic dyes. Moreover, the dye solution adsorbed by AC-JE fibers exhibits an ideal freshwater quality (almost no bacteria), similar to that of the deionized water. The AC-JE fibers prove their potential for dye removal, in both adsorption and filtration. Their sterilization ability substantiates their potential in the field of water purification as they can be used as ideal absorbents based on cellulose for removing dyes and purifying wastewater.

Blackbody-Inspired Array Structural Polypyrrole-Sunflower Disc with Extremely High Light Absorption for Efficient Photothermal Evaporation.

The three-dimensional (3D) structural design of solar evaporators has been considered as one of the most promising approaches toward enhancing photothermal performance by improving light absorption and the available evaporation area. Herein, polypyrrole-decorated 3D array structural sunflower discs (PPy-SFD) were prepared for solar steam generation, thereby turning SFD biomass waste into valuable materials. The SFD can absorb a majority of the incident light because of numerous light reflections from each natural 3D array structural unit, and therefore behaves similar to a blackbody. Moreover, a facile pyrrole polymerization method was introduced to further improve SFD light absorption and enhance the photothermal performance of SFD. This circumvents expensive consumption fabrication processes. The black PPy-decorated SFD shows a light absorption of 99.3% across the entire solar spectrum coupled with mechanical stability. During photothermal evaporation, the increased evaporation area of the 3D array structural SFD could effectively reduce heat loss to the environment because the inherent microporous structure of the SFD leaves and cellulose hydrophilicity provide channels for water transport. The PPy-SFD-based evaporator could reach an evaporation rate of 1.74 kg m-2 h-1 under 1 sun. Thus, the 3D array structural PPy-SFD is a possible candidate for high-efficiency photothermal evaporators.

Giant enhancement and anomalous thermal hysteresis of saturation moment in magnetic nanoparticles embedded in multiwalled carbon nanotubes.

We report high-energy synchrotron X-ray diffraction spectrum and high-temperature magnetic data for multiwalled carbon nanotubes (MWCNTs) embedded with Fe and Fe3O4 nanoparticles. We unambiguously show that the saturation moments of the embedded Fe and Fe3O4 nanoparticles are enhanced by a factor of about 3.0 compared with what would be expected if they would be unembedded. More intriguingly the enhanced moments were completely lost when the sample was heated up to 1120 K, and the lost moments were completely recovered through two more thermal cycles below 1020 K. These novel results cannot be explained by the magnetism of the Fe and Fe3O4 impurity phases, the magnetic proximity effect between magnetic nanoparticles and carbon, and the ballistic transport of MWCNTs.

Temperature dependence of magnetic anisotropy constant in iron chalcogenide Fe(3)Se(4): Excellent agreement with theories.

Magnetic hysteresis loops were measured for ferrimagnetic iron chalcogenide [Formula: see text] nanoparticles in the whole temperature range below the Curie temperature [Formula: see text] (315 K). The coercivity of the material is huge, reaching about 40 kOe at 10 K. The magnetic anisotropy constant K was determined from the magnetic hysteresis loop using the law of approach to saturation. The deduced anisotropy constant at 10 K is [Formula: see text], which is over one order of magnitude larger than that of [Formula: see text]. We also demonstrated that the experimental magnetic hysteresis loop is in good agreement with the theoretical curve calculated by Stoner and Wohlfarth for a noninteracting randomly oriented uniaxial single-domain particle system. Moreover, we show that K is proportional to the cube of the saturation magnetization [Formula: see text], which confirms earlier theoretical models for uniaxial magnets.

Specific heat evidence for bulk s-wave gap symmetry of optimally electron-doped Pr(1.85)Ce(0.15)CuO(4-y) superconductors.

We reanalyze specific heat data for optimally electron-doped Pr(1.85)Ce(0.15)CuO(4-y) superconductors. The magnetic field dependence of the electronic specific heat in the vortex state does not support d-wave gap symmetry but agrees quantitatively with an s-wave theory. Furthermore, the field dependence at a finite temperature almost coincides with that for a conventional s-wave superconductor, Vi(3)Si. The present work provides bulk evidence for a nodeless s-wave gap symmetry in optimally electron-doped cuprates.

Fine structure in the tunneling spectra of electron-doped cuprates: no coupling to the magnetic resonance mode.

We reanalyze high-resolution scanning tunneling spectra of the electron-doped cuprate Pr(0.88)LaCe(0.12)CuO(4) (T(c) = 24 K). We find that the spectral fine structure below 35 meV is consistent with strong coupling to a bosonic mode at about 16 meV, in quantitative agreement with early tunneling spectra of Nd(1.85)Ce(0.15)CuO(4). Since the energy of the bosonic mode is significantly higher than that (9.5-11 meV) of the magnetic resonancelike mode observed by inelastic neutron scattering, the coupling feature at about 16 meV cannot arise from strong coupling to the magnetic mode. The present work thus demonstrates that the magnetic resonancelike mode cannot be the origin of high-temperature superconductivity in electron-doped cuprates.