ZhiChao Wang

Bio: ZhiChao Wang is an academic researcher from Kobe University. The author has contributed to research in topics: Receptor tyrosine kinase & Frizzled. The author has an hindex of 2, co-authored 2 publications receiving 8896 citations.

Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

Abstract: Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.

Ror2/Frizzled Complex Mediates Wnt5a-Induced AP-1 Activation by Regulating Dishevelled Polymerization

Abstract: The receptor tyrosine kinase Ror2 acts as a receptor or coreceptor for Wnt5a to mediate Wnt5a-induced activation of the Wnt/JNK pathway and inhibition of the β-catenin-dependent canonical Wnt pathway. However, little is known about how Ror2 cooperates with another receptor component(s) to mediate Wnt5a signaling. We show here that Ror2 regulates Wnt5a-induced polymerization of Dishevelled (Dvl) and that this Ror2-mediated regulation of Dvl is independent of the cytoplasmic region of Ror2. Ror2 can associate with Frizzled7 (Fz7) via its extracellular cysteine-rich domain to form a receptor complex that is required for the regulation of Dvl and activation of the AP-1 promoter after Wnt5a stimulation. Suppressed expression of Fz7 indeed results in the inhibition of Wnt5a-induced polymerization of Dvl and AP-1 activation. Interestingly, both the DIX and the DEP domains of Dvl are indispensable for Dvl polymerization and subsequent AP-1 activation after Wnt5a stimulation. We further show that polymerized Dvl is colocalized with Rac1 and that suppressed expression of Rac1 inhibits Wnt5a-induced AP-1 activation. Collectively, our results indicate that Ror2/Fz receptor complex plays an important role in the Wnt5a/Rac1/AP-1 pathway by regulating the polymerization of Dvl.

Campylobacter jejuni Cytolethal Distending Toxin Induces GSDME-Dependent Pyroptosis in Colonic Epithelial Cells

Abstract: Background Cytolethal distending toxin (CDT) is a critical virulence factor of Campylobacter jejuni, and it induces cell death and regulates inflammation response in human epithelial cells. Pyroptosis is an inflammatory form of programmed cell death (PCD), but whether it is involved in CDT-mediated cytotoxicity remains elusive. Aims This study explores the role and mechanism of pyroptosis in CDT-mediated cytotoxicity. Methods HCT116 and FHC cell lines were treated with CDT. Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability. Western blotting was used to measure the expression of related proteins in the pathway, and cell morphology observation, annexin V/propidium iodide (PI) staining and lactate dehydrogenase (LDH) release assay were performed to evaluate the occurrence of pyroptosis. Result Our results show that C. jejuni CDT effectively induces pyroptosis in a dose- and time- dependent manner in human colonic epithelial cells owing to its DNase activity. Specific pyroptotic features including large bubbles emerging from plasma membrane and LDH release were observed upon CDT treatment. Moreover, CDT-induced pyroptosis involves the caspase-9/caspase-3 axis, which is followed by gasdermin E (GSDME) cleavage rather than gasdermin D (GSDMD). N-acetyl cysteine (NAC), a reactive oxygen species (ROS) inhibitor, attenuates the activation of caspase-9/3, the cleavage of GSDME and pyroptotic characteristic, therefore demonstrating ROS initiates pyroptotic signaling. Conclusions We first clarify a molecular mechanism that CDT induces pyroptosis via ROS/caspase-9/caspase-3/GSDME signaling. These findings provide a new insight on understanding of CDT-induced pathogenesis at the molecular level.

Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

Abstract: Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.

Engineering precision nanoparticles for drug delivery

Abstract: In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

The complex world of WNT receptor signalling

Abstract: 30 years after the identification of WNTs, their signal transduction has become increasingly complex, with the discovery of more than 15 receptors and co-receptors in seven protein families. The recent discovery of three receptor classes for the R-spondin family of WNT agonists further adds to this complexity. What emerges is an intricate network of receptors that form higher-order ligand-receptor complexes routing downstream signalling. These are regulated both extracellularly by agonists such as R-spondin and intracellularly by post-translational modifications such as phosphorylation, proteolytic processing and endocytosis.

Targeting the NLRP3 inflammasome in inflammatory diseases

Abstract: Danger signals are a hallmark of many common inflammatory diseases, and these stimuli can function to activate the cytosolic innate immune signalling receptor NLRP3 (NOD-, LRR- and pyrin domain-containing 3). Once activated, NLRP3 nucleates the assembly of an inflammasome, leading to caspase 1-mediated proteolytic activation of the interleukin-1β (IL-1β) family of cytokines, and induces an inflammatory, pyroptotic cell death. Pharmacological inhibition of NLRP3 activation results in potent therapeutic effects in a wide variety of rodent models of inflammatory diseases, effects that are mirrored by genetic ablation of NLRP3. Although these findings highlight the potential of NLRP3 as a drug target, an understanding of NLRP3 structure and activation mechanisms is incomplete, which has hampered the discovery and development of novel therapeutics against this target. Here, we review recent advances in our understanding of NLRP3 activation and regulation, highlight the evolving landscape of NLRP3 modulators and discuss opportunities for pharmacologically targeting NLRP3 with novel small molecules.

Flexible Electronics: Stretchable Electrodes and Their Future

Abstract: Flexible electronics, as an emerging and exciting research field, have brought great interest to the issue of how to make flexible electronic materials that offer both durability and high performance at strained states. With the advent of on-body wearable and implantable electronics, as well as increasing demands for human-friendly intelligent soft robots, enormous effort is being expended on highly flexible functional materials, especially stretchable electrodes, by both the academic and industrial communities. Among different deformation modes, stretchability is the most demanding and challenging. This review focuses on the latest advances in stretchable transparent electrodes based on a new design strategy known as kirigami (the art of paper cutting) and investigates the recent progress on novel applications, including skin-like electronics, implantable biodegradable devices, and bioinspired soft robotics. By comparing the optoelectrical and mechanical properties of different electrode materials, some of the most important outcomes with comments on their merits and demerits are raised. Key design considerations in terms of geometries, substrates, and adhesion are also discussed, offering insights into the universal strategies for engineering stretchable electrodes regardless of the material. It is suggested that highly stretchable and biocompatible electrodes will greatly boost the development of next-generation intelligent life-like electronics.