Despite many efforts to develop hormone therapy and chemotherapy, no effective strategy to suppress prostate cancer metastasis has been established because the metastasis is not well understood. We ...here investigate a role of CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) in prostate cancer metastasis. CITED2 is highly expressed in metastatic prostate cancer, and its expression is correlated with poor survival. The CITED2 gene is highly activated by ETS-related gene that is overexpressed due to chromosomal translocation. CITED2 acts as a molecular chaperone to guide PRMT5 and p300 to nucleolin, thereby activating nucleolin. Informatics and experimental data suggest that the CITED2-nucleolin axis is involved in prostate cancer metastasis. This axis stimulates cell migration through the epithelial-mesenchymal transition and promotes cancer metastasis in a xenograft mouse model. Our results suggest that CITED2 plays a metastasis-promoting role in prostate cancer and thus could be a target for preventing prostate cancer metastasis.
Dendrites are ubiquitous crystals produced in supersaturated solutions and supercooled melts, but considerably less is known about their formation and growth kinetics. Here, the key factors are ...explored that dictate dendrite formation and growth, utilizing experimental colloidal models in which the particles act as molecules with Mie potential. Depletion attraction is employed to colloids and manipulate their strength to control supersaturation. Dendrites are predominantly produced under conditions of low supersaturation, where the separation between crystals is large due to slow nucleation. The dendrites do not emerge directly from nuclei. Instead, isotropic grains, initially produced from nuclei, morph into polygons. Arms then sprout from the vertices of these polygons, eventually giving rise to dendrites. Triggering this polygon‐to‐dendrite transformation requires a high diffusional flux. This necessitates a prolonged diffusion time to maintain a steep concentration gradient in the surrounding environment even after the transformation from circular grains to polygons.
Dendritic crystals are produced by depletion‐mediated spontaneous assembly of colloids at low supersaturation. The low supersaturation causes slow nucleation, which gives large separation between crystals, ensuring a prolonged diffusion time to maintain a steep concentration gradient. The crystals initially take isotropic grains, morph into polygons, and eventually giving rise to dendrites by sprouting arms from the vertices of the polygons.
Cholesteric liquid crystals (CLCs), also known as chiral nematic LCs, show a photonic stopband, which is promising for various optical applications. In particular, CLCs confined in microcompartments ...are useful for sensing, lasing, and optical barcoding at the microscale. The integration of distinct CLCs into single microstructures can provide advanced functionality. In this work, CLC multishells with multiple stopbands are created by liquid–liquid phase separation (LLPS) in a simple yet highly controlled manner. A homogeneous ternary mixture of LC, hydrophilic liquid, and co‐solvent is microfluidically emulsified to form uniform oil‐in‐water drops, which undergo LLPS to form onion‐like drops composed of alternating CLC‐rich and CLC‐depleted layers. The multiplicity is controlled from one to five by adjusting the initial composition of the ternary mixture, which dictates the number of consecutive steps of LLPS. Interestingly, the concentration of the chiral dopant becomes reduced from the outermost to the innermost CLC drop due to uneven partitioning during LLPS, which results in multiple stopbands. Therefore, the photonic multishells show multiple structural colors. In addition, dye‐doped multishells provide band‐edge lasing at two different wavelengths. This new class of photonic multishells will provide new opportunities for advanced optical applications.
Photonic multishells are created by controlled phase separation of cholesteric liquid crystals and hydrophilic liquid confined in emulsion drops. The material exchange between the dispersed and continuous phases triggers the consecutive steps of phase separation, through which onion‐like drops are formed. Multiple photonic stopbands are spontaneously developed by uneven partitioning of the chiral dopant, which provides advanced photonic functionality.
Technologies to monitor microenvironmental conditions and its spatial distribution are in high demand, yet remain unmet need. Herein, photonic microsensors are designed in a capsule format that can ...be injected, suspended, and implanted in any target volume. Colorimetric sensors are loaded in the core of microcapsules by assembling core–shell colloids into crystallites through the depletion attraction. The shells of the colloids are made of a temperature‐responsive hydrogel, which enables the crystallites to rapidly and widely tune the structural color in response to a change in temperature while maintaining close‐packed arrays. The spherical symmetry of the microcapsules renders them optically isotropic, i.e., displaying orientation‐independent color. In addition, as a solid membrane is used to protect the delicate crystallites from external stresses, their high stability is assured. More importantly, each microcapsule reports the temperature of its microenvironment so that a suspension of capsules can provide information on the spatial distribution of the temperature.
Photonic capsule sensors are designed by assembling thermoresponsive colloids to crystallites in the core of double‐emulsion drops through the depletion attraction. The close‐packed lattice of the crystallite enables wide and rapid color tuning and the capsule membrane protects the delicate crystallites from external stresses. The capsule sensors, which can be injected, suspended, and implanted, are promising for monitoring the microenvironmental temperature and its spatial distribution.
Colloidal crystals display photonic stopbands that generate reflective structural colors. While micropatterning offers significant value for various applications, the resolution is somewhat limited ...for conventional top‐down approaches. In this work, a simple, single‐step bottom‐up approach is introduced to produce photonic micropatterns through depletion‐mediated regioselective growth of colloidal crystals. Lithographically‐featured micropatterns with planar surfaces and nano‐needle arrays as substrates are employed. Heterogeneous nucleation is drastically suppressed on nano‐needle arrays due to minimal particle‐to‐needles overlap of excluded volumes, while it is promoted on planar surfaces with large particle‐to‐plane volume overlap, enabling regioselective growth of colloidal crystals. This strategy allows high‐resolution micropatterning of colloidal photonic crystals, with a minimum feature size as small as 10 µm. Stopband positions, or structural colors, are controllable through concentration and depletant and salt, as well as particle size. Notably, secondary colors can be created through structural color mixing by simultaneously crystallizing two different particle sizes into their own crystal grains, resulting in two distinct reflectance peaks at controlled wavelengths. The simple and highly reproducible method for regioselective colloidal crystallization provides a general route for designing elaborate photonic micropatterns suitable for various applications.
Photonic micropatterns are created through single‐step growth of colloidal crystals on lithographically prepatterned substrates with planar surfaces and nano‐needle arrays. When the colloidal assembly is mediated by depletion attraction, the planar surfaces effectively cause heterogeneous nucleation and crystal growth, whereas the nano‐needle arrays inhibit it. This results in regioselective crystallization on the planar areas, yielding high‐resolution structural‐color graphics.
Colloidal crystals are designed as photonic microparticles for various applications. However, conventional microparticles generally have only one stopband from a single lattice constant, which ...restricts the range of colors and optical codes available. Here, photonic microcapsules are created that contain two or three distinct crystalline grains, resulting in dual or triple stopbands that offer a wider range of colors through structural color mixing. To produce distinct colloidal crystallites from binary or ternary colloidal mixtures, the interparticle interaction is manipulated using depletion forces in double-emulsion droplets. Aqueous dispersions of binary or ternary colloidal mixtures in the innermost droplet are gently concentrated in the presence of a depletant and salt by imposing hypertonic conditions. Different-sized particles crystallize into their own crystals rather than forming random glassy alloys to minimize free energy. The average size of the crystalline grains can be adjusted with osmotic pressure, and the relative ratio of distinct grains can be controlled with the mixing ratio of particles. The resulting microcapsules with small grains and high surface coverage are almost optically isotropic and exhibit highly-saturated mixed structural colors and multiple reflectance peaks. The mixed color and reflectance spectrum are controllable with the selection of particle sizes and mixing ratios.
Photonic microbeads containing crystalline colloidal arrays are promising as a key component of structural‐color inks for various applications including printings, paintings, and cosmetics. However, ...structural colors from microbeads usually have low color saturation and the production of the beads requires delicate and time‐consuming protocols. Herein, elastic photonic microbeads are designed with enhanced color saturation through facile photocuring of oil‐in‐oil emulsion droplets. Dispersions of highly‐concentrated silica particles in elastomer precursors are microfluidically emulsified into immiscible oil to produce monodisperse droplets. The silica particles spontaneously form crystalline arrays in the entire volume of the droplets due to interparticle repulsion which is unperturbed by the diffusion of the surrounding oil whereas weakened for oil‐in‐water droplets. The crystalline arrays are permanently stabilized by photopolymerization of the precursor, forming elastic photonic microbeads. The microbeads are transferred into the refractive‐index‐matched biocompatible oil. The high crystallinity of colloidal arrays increases the reflectivity at stopband and the index matching reduces incoherent scattering at the surface of the microbeads, enhancing color saturation. The colors can be adjusted by mixing two distinctly colored microbeads. Also, low stiffness and high elasticity reduce foreign‐body sensation and enhance fluidity, potentially serving as pragmatic structural colorants for photonic inks.
Elastic photonic microbeads with high color saturation are produced by employing oil‐in‐oil emulsion droplets. As the continuous oil phase does not lessen the interparticle repulsion, particles form crystalline arrays in the entire volume. In addition, refractive‐index matching further reduces incoherent scattering. High color saturation and elasticity render the microbeads promising as structural colorants in cosmetics and inks.
The photonic cross-communication between photonic droplets has provided complex color patterns through multiple reflections, potentially serving as novel optical codes. However, the ...cross-communication is mostly restricted to symmetric pairs of identical droplets. Here, a design rule is reported for the asymmetric pairing of two distinct droplets to provide bright color patterns through strong cross-communication and enrich a variety of optical codes. Cholesteric liquid crystal (CLC) droplets with different stopband positions and sizes are paired. The brightness of corresponding color patterns is maximized when the pairs are selected to effectively guide light along the double reflection path by stopbands of two droplets. The experimental results are in good agreement with a geometric model where the blueshift of stopbands is better described by the angles of refraction rather than reflection. The model predicts the effectiveness of pairing quantitatively, which serves as a design rule for programming the asymmetric photonic cross-communication. Moreover, three distinct droplets can be paired in triangular arrays, where all three cross-communication paths yield bright color patterns when three droplets are selected to simultaneously satisfy the rule. It is believed that asymmetric pairing of distinct CLC droplets opens new opportunities for programmable optical encoding in security and anti-counterfeiting applications.
The prolyl hydroxylase domain-containing proteins (PHD1-3) and the asparaginyl hydroxlyase factor inhibiting HIF (FIH) are oxygen sensors for hypoxia-inducible factor-driven transcription of ...hypoxia-induced genes, but whether these sensors affect oxygen-dependent epigenetic regulation more broadly is not known. Here, we show that FIH exerts an additional role as an oxygen sensor in epigenetic control by the histone lysine methyltransferases G9a and GLP. FIH hydroxylated and inhibited G9a and GLP under normoxia. When the FIH reaction was limited under hypoxia, G9a and GLP were activated and repressed metastasis suppressor genes, thereby triggering cancer cell migration and peritoneal dissemination of ovarian cancer xenografts. In clinical specimens of ovarian cancer, expression of FIH and G9a were reciprocally associated with patient outcomes. We also identified mutations of FIH target motifs in G9a and GLP, which exhibited excessive H3K9 methylation and facilitated cell invasion. This study provides insight into a new function of FIH as an upstream regulator of oxygen-dependent chromatin remodeling. It also implies that the FIH-G9a/GLP pathway could be a potential target for inhibiting hypoxia-induced cancer metastasis.
These findings deepen understanding of oxygen-dependent gene regulation and cancer metastasis in response to hypoxia.
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The fibroblast growth factor receptor 2 (FGFR2) is a membrane receptor that promotes cell proliferation and differentiation. FGFR2 is also present in the nucleus, which raises a question on a new ...role of FGFR2 in regulating gene expression. Hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2) are nuclear proteins that transactivate many genes essential for cancer survival and metastasis under hypoxic conditions. Here, we investigated if nuclear FGFR2 modulates the HIF-driven hypoxic response. Using the TCGA database, we found that FGFR2 downregulation is associated with poor prognosis in prostate cancer. A gene-set enrichment analysis showed that metastasis- and hypoxia-related genes are associated with a low expression of FGFR2 in prostate cancer. Thus, we tested the possibility that FGFR2 negatively regulates the hypoxia-triggered metastasis of prostate cancer. FGFR2 controls migration and invasion of prostate cancer cells under hypoxia by inhibiting the HIF-driven gene expression. FGFR2 and HIF proteins co-localize and associate in the nucleus under hypoxia. FGFR2 interacts with the transactivation domain of HIF-1α and blocks the recruitment of coactivator p300, resulting in repression of HIF target genes. Based on these results, we propose a novel function of FGFR2 as a metastasis suppressor by controlling HIF-mediated hypoxic responses.
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