EphA10 (erythropoietin‐producing hepatocellular carcinoma receptor A10) is a catalytically defective receptor protein tyrosine kinase in the ephrin receptor family. Although EphA10 is involved in the ...malignancy of some types of cancer, its role as an oncogene has not been extensively studied. Here, we investigated the influence of EphA10 on the tumorigenic potential of pancreatic cancer cells. Analysis of expression profiles from The Cancer Genome Atlas confirmed that EphA10 was elevated and higher in tumor tissues than in normal tissues in some cancer types, including pancreatic cancer. EphA10 silencing reduced the proliferation, migration, and adhesion of MIA PaCa‐2 and AsPC‐1 pancreatic cancer cells. These effects were reversed by overexpression of EphA10 in MIA PaCa‐2 cells. Importantly, overexpression and silencing of EphA10 respectively increased and decreased the weight, volume, and number of Ki‐67‐positive proliferating cells in MIA PaCa‐2 xenograft tumors. Further, EphA10 expression was positively correlated with invasion and gelatin degradation in MIA PaCa‐2 cells. Moreover, overexpression of EphA10 enhanced the expression and secretion of MMP‐9 in MIA PaCa‐2 cells and increased the expression of MMP‐9 and the vascular density in xenograft tumors. Finally, expression of EphA10 increased the phosphorylation of ERK, JNK, AKT, FAK, and NF‐κB, which are important for cell proliferation, survival, adhesion, migration, and invasion. Therefore, we suggest that EphA10 plays a pivotal role in the tumorigenesis of pancreatic epithelial cells and is a novel therapeutic target for pancreatic cancer.
The role of a catalytically defective receptor protein tyrosine kinase EphA10 for tumorigenesis has been investigated in pancreatic cancer cells. Overexpression and knockdown of EphA10 respectively increased and decreased the proliferation, migration, adhesion, and invasion of MIA PaCa‐2 and AsPC‐1 pancreatic cancer cells as well as the weight and volume of MIA PaCa‐2 xenograft tumors. Our data suggest that EphA10 plays a pivotal role in tumorigenesis of pancreatic epithelial cells and is a novel therapeutic target for pancreatic cancer.
Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase (RPTK), plays an oncogenic role by activating an unidentified TKI‐258 (dovitinib)‐sensitive RPTK in ...esophageal squamous cell carcinoma (ESCC) cells. Here, we demonstrate that among TKI‐258‐sensitive RPTKs, fibroblast growth factor receptor (FGFR) 1 is significantly up‐regulated in ESCC tissues and cell lines. We show that PTK7 colocalizes with FGFR1 and binds it via its extracellular domain in human embryonic kidney 293 and ESCC TE‐10 cells. PTK7 knockdown not only reduced ligand‐free and fibroblast growth factor (FGF)‐induced phosphorylation of FGFR1 but also the interaction of signaling adaptor proteins with FGFR1 and activation of downstream signaling proteins in TE‐10 cells. In addition, PTK7 knockdown reduced FGF‐induced oncogenic phenotypes including proliferation, anchorage‐independent colony formation, wound healing, and invasion in ESCC cells. Taken together, our data demonstrate that PTK7 binds and activates FGFR1 independent of FGF and thus increases oncogenicity of PTK7‐ and FGFR1‐positive cancers such as ESCC.—Shin, W.‐S., Lee, H. W., Lee, S.‐T. Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF. FASEB J. 33, 12960–12971 (2019). www.fasebj.org
Crystal engineering based on σ‐hole interactions is an emerging approach for realization of new materials with higher complexity. Neutral inorganic clusters derived from ...1,2‐dicarba‐closo‐dodecaborane, substituted with ‐SeMe, ‐TeMe, and ‐I moieties on both skeletal carbon vertices are experimentally demonstrated herein as outstanding chalcogen‐ and halogen‐bond donors. In particular, these new molecules strongly interact with halide anions in the solid‐state. The halide ions are coordinated by one or two donor groups (μ1‐ and μ2‐coordinations), to stabilize a discrete monomer or dimer motifs to 1D supramolecular zig‐zag chains. Crucially, the observed chalcogen bond and halogen bond interactions feature remarkably short distances and high directionality. Electrostatic potential calculations further demonstrate the efficiency of the carborane derivatives, with Vs,max being similar or even superior to that of reference organic halogen‐bond donors, such as iodopentafluorobenzene.
Substituted carboranes with ‐SeMe, ‐TeMe, and ‐I groups on the skeletal carbon vertices are shown to be outstanding chalcogen bond (ChB) and halogen bond (XB) donors to recognize halide anions. Moreover, the interactions are found to be remarkably efficient with short distances and high directionality. Theoretical calculations further validate the presence of a deep σ‐hole on Se, Te, and I.
Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to ...elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in
knockout (KO) mice following treatment with AEW. The increase in the intracellular calcium levels by TSLP in the dorsal root ganglia (DRG) of
KO mice was also significantly attenuated. The spontaneous scratching bouts were significantly decreased in both the HC067047-treated and
KO AEW mice. Importantly, the TSLP-dependent release of tryptase from the mast cells was significantly reduced in both the HC067047-treated mice and
KO AEW mice. Notably, inhibition of the TSLP-induced signaling pathway in DRG selectively reduced the spontaneous scratching bouts in AEW mice. Overall, the results demonstrated that the cutaneous neuroimmune interactions of TSLP and TRPV4 play pivotal roles in dry skin-induced pruritus.
The rapid detection of biological and chemical substances in real time is particularly important for public health and environmental monitoring and in the military sector. If the process of substance ...detection to visual reporting can be implemented into a single miniaturized sensor, there could be a profound impact on practical applications. Here, we propose a compact sensor platform that integrates liquid crystals (LCs) and holographic metasurfaces to autonomously sense the existence of a volatile gas and provide an immediate visual holographic alarm. By combining the advantage of the rapid responses to gases realized by LCs with the compactness of holographic metasurfaces, we develop ultracompact gas sensors without additional complex instruments or machinery to report the visual information of gas detection. To prove the applicability of the compact sensors, we demonstrate a metasurface-integrated gas sensor on safety goggles via a one-step nanocasting process that is attachable to flat, curved, and flexible surfaces.
Endophytic fungi are known plant symbionts. They produce a variety of beneficial metabolites for plant growth and survival, as well as defend their hosts from attack of certain pathogens. Coastal ...dunes are nutrient deficient and offer harsh, saline environment for the existing flora and fauna. Endophytic fungi may play an important role in plant survival by enhancing nutrient uptake and producing growth-promoting metabolites such as gibberellins and auxins. We screened roots of Ixeris repenes (L.) A. Gray, a common dune plant, for the isolation of gibberellin secreting endophytic fungi.
We isolated 15 endophytic fungi from the roots of Ixeris repenes and screened them for growth promoting secondary metabolites. The fungal isolate IR-3-3 gave maximum plant growth when applied to waito-c rice and Atriplex gemelinii seedlings. Analysis of the culture filtrate of IR-3-3 showed the presence of physiologically active gibberellins, GA1, GA3, GA4 and GA7 (1.95 ng/ml, 3.83 ng/ml, 6.03 ng/ml and 2.35 ng/ml, respectively) along with other physiologically inactive GA5, GA9, GA12, GA15, GA19, GA20 and, GA24. The plant growth promotion and gibberellin producing capacity of IR-3-3 was much higher than the wild type Gibberella fujikuroi, which was taken as control during present study. GA5, a precursor of bioactive GA3 was reported for the first time in fungi. The fungal isolate IR-3-3 was identified as a new strain of Penicillium citrinum (named as P. citrinum KACC43900) through phylogenetic analysis of 18S rDNA sequence.
Isolation of new strain of Penicillium citrinum from the sand dune flora is interesting as information on the presence of Pencillium species in coastal sand dunes is limited. The plant growth promoting ability of this fungal strain may help in conservation and revegetation of the rapidly eroding sand dune flora. Penicillium citrinum is already known for producing mycotoxin citrinin and cellulose digesting enzymes like cellulase and endoglucanase, as well as xylulase. Gibberellins producing ability of this fungus and the discovery about the presence of GA5 will open new aspects of research and investigations.
Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, ...smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca(2+)-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.
Flammulina velutipes is a fungus with health and medicinal benefits that has been used for consumption and cultivation in East Asia. F. velutipes is also known to degrade lignocellulose and produce ...ethanol. The overlapping interests of mushroom production and wood bioconversion make F. velutipes an attractive new model for fungal wood related studies. Here, we present the complete sequence of the F. velutipes genome. This is the first sequenced genome for a commercially produced edible mushroom that also degrades wood. The 35.6-Mb genome contained 12,218 predicted protein-encoding genes and 287 tRNA genes assembled into 11 scaffolds corresponding with the 11 chromosomes of strain KACC42780. The 88.4-kb mitochondrial genome contained 35 genes. Well-developed wood degrading machinery with strong potential for lignin degradation (69 auxiliary activities, formerly FOLymes) and carbohydrate degradation (392 CAZymes), along with 58 alcohol dehydrogenase genes were highly expressed in the mycelium, demonstrating the potential application of this organism to bioethanol production. Thus, the newly uncovered wood degrading capacity and sequential nature of this process in F. velutipes, offer interesting possibilities for more detailed studies on either lignin or (hemi-) cellulose degradation in complex wood substrates. The mutual interest in wood degradation by the mushroom industry and (ligno-)cellulose biomass related industries further increase the significance of F. velutipes as a new model.
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