A5003421949- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Gastric Cancer Management and Outcomes
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Microtubule and mitosis dynamics
- Force Microscopy Techniques and Applications
- Antimicrobial agents and applications
- Wnt/β-catenin signaling in development and cancer
- Cell death mechanisms and regulation
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Lipid Membrane Structure and Behavior
- Gastrointestinal Tumor Research and Treatment
- Protease and Inhibitor Mechanisms
- RNA Research and Splicing
- Skin and Cellular Biology Research
- Signaling Pathways in Disease
- Erythrocyte Function and Pathophysiology
- Metastasis and carcinoma case studies
- Biopolymer Synthesis and Applications
- Caveolin-1 and cellular processes
- Hippo pathway signaling and YAP/TAZ
- Pancreatic and Hepatic Oncology Research
Sasaki Institute
2017-2025
Osaka Gas (Japan)
2024
Showa University Hospital
2019
National Cancer Centre Japan
2011-2015
Kyoto Research Park
2013-2015
Tokyo University of Pharmacy and Life Sciences
2007-2013
The University of Tokyo
2000-2013
National Cancer Center Hospital East
2012
Kyoto University
2012
Japan Science and Technology Agency
2001-2011
Invadopodia are actin-rich membrane protrusions with a matrix degradation activity formed by invasive cancer cells. We have studied the molecular mechanisms of invadopodium formation in metastatic carcinoma Epidermal growth factor (EGF) receptor kinase inhibitors blocked presence serum, and EGF stimulation serum-starved cells induced formation. RNA interference dominant-negative mutant expression analyses revealed that neural WASP (N-WASP), Arp2/3 complex, their upstream regulators, Nck1,...
Invadopodia are matrix-degrading membrane protrusions in invasive carcinoma cells. The mechanisms regulating invadopodium assembly and maturation not understood. We have dissected the stages of show that invadopodia use cortactin phosphorylation as a master switch during these processes. In particular, was found to regulate cofilin Arp2/3 complex–dependent actin polymerization. Cortactin directly binds inhibits its severing activity. is required release this inhibition so can sever filaments...
Invadopodia are proteolytic membrane protrusions formed by highly invasive cancer cells, commonly observed on substrate(s) mimicking extracellular matrix. Although invadopodia proposed to have roles in invasion and metastasis, direct evidence has not been available. We previously reported that neural Wiskott–Aldrich syndrome protein (N-WASP), a member of WASP family proteins regulate reorganization the actin cytoskeleton, is an essential component invadopodia. Here, we report N-WASP-mediated...
Invadopodia are ventral membrane protrusions through which invasive cancer cells degrade the extracellular matrix. They thought to function in migration of tissue barriers, is necessary for invasion and metastasis. Although many protein components invadopodia have been identified, organization role lipids not well understood. In this study, lipid rafts, cholesterol-enriched microdomains, assembly human breast was investigated. Lipid rafts enriched, internalized, dynamically trafficked at...
Acrylate monomers with pendant biguanide groups were successfully synthesized, and their homopolymers copolymers prepared acrylamide. These cationic disinfectants of polymeric forms exhibited high antibacterial activity against gram-positive bacteria, whereas they less active gram-negative bacteria. It was found that the much higher than monomeric species, difference in between polymers discussed on basis contributions to each elementary process lethal action.
Two types of polycations with pendant active groups were synthesized: one is polymethacrylate containing biguanide units, and the other poly(vinylbenzyl ammonium chloride). The two found to exhibit higher bactericidal activity against Staphylococcus aureus than corresponding monomers. Fractionation was successfully performed on gel filtration chromatography, examination antibacterial S. well-characterized polymer samples various molecular weights (MW) revealed that strongly dependent MW...
We examined the role of actin nucleation promoters neural Wiskott-Aldrich syndrome protein (N-WASP) and WAVE2 in cell protrusion response to epidermal growth factor (EGF), a key regulator carcinoma invasion. found that knockdown (KD) suppresses lamellipod formation increases filopod formation, whereas N-WASP KD has no effect. However, simultaneous both proteins results large jagged protrusions with lamellar properties increased formation. This suggests another activity is at work cells EGF....
Invadopodia are extracellular matrix-degrading protrusions formed by invasive cancer cells that thought to function in invasion. Although many invadopodia components have been identified, signaling pathways link stimuli formation remain largely unknown. We investigate the role of phosphoinositide 3-kinase (PI3K) during formation. find human breast cells, both and degradation a gelatin matrix were blocked treatment with PI3K inhibitors or sequestration D-3 phosphoinositides. Functional...
Metastatic mammary carcinoma cells, which have previously been observed to form mature, matrix degrading invadopodia on a thick ECM matrix, are able with similar characteristics glass without applied matrix. They in response epidermal growth factor (EGF), and contain the usual invadopodium core proteins N-WASP, Arp2/3, cortactin, cofilin, F-actin. The study of allows for higher resolution analysis including use total internal reflection microscopy their relationship other cell motility...
It has been demonstrated that the actin-severing activity of cofilin can be downregulated by LIM kinase (LIMK)-dependent phosphorylation at residue Ser3. Chemotactic stimulation in various cell types induces dephosphorylation, suggesting activation these cells occurs a dephosphorylation mechanism. However, resting metastatic carcinoma have majority their dephosphorylated but largely inactive state. Stimulation with epidermal growth factor (EGF) an increase after 60 seconds together...
Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous (WAVE) proteins play a major role in Rac-induced actin dynamics, but Rac does not bind directly to WAVE proteins. It has been proposed that either the insulin receptor substrate 53 (IRSp53) or complex of containing Abelson interactor 1 (Abi1) mediates interaction WAVE2 and Rac. Depletion endogenous IRSp53 by RNA-mediated interference (RNAi) RAW/LR5 macrophage cell line resulted significant reduction Rac1Q61L-induced surface...
All WASP family proteins share a common C terminus that consists of the verprolin homology domain (V), cofilin (C), and acidic region (A), through which they activate Arp2/3 complex-induced actin polymerization. In this study, we characterized complex-mediated polymerization activity VCA fragments all proteins: WASP, N-WASP, WAVE1, WAVE2, WAVE3. stimulated nucleating complex. Among them, N-WASP VCA, possesses two tandem V motifs, had more potent than other proteins. The chimeric protein...
Neural Wiskott-Aldrich syndrome protein (N-WASP) is an actin-regulating that induces filopodium formation downstream of Cdc42. It has been shown filopodia actively extend from the growth cone, a guidance apparatus located at tip neurites, suggesting their role in neurite extension. Here we examined possible involvement N-WASP extension process. Since verprolin, cofilin homology and acidic region (VCA) known to be required for activation Arp2/3 complex actin polymerization, prepared mutant...