A5085007436- Cancer Cells and Metastasis
- Fibroblast Growth Factor Research
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- MicroRNA in disease regulation
- Cytokine Signaling Pathways and Interactions
- HER2/EGFR in Cancer Research
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related molecular mechanisms research
- Cancer-related Molecular Pathways
- Wnt/β-catenin signaling in development and cancer
- Retinal Diseases and Treatments
- Epigenetics and DNA Methylation
- Gene expression and cancer classification
- Protein Tyrosine Phosphatases
- PI3K/AKT/mTOR signaling in cancer
- Bioinformatics and Genomic Networks
- Lung Cancer Research Studies
- Glaucoma and retinal disorders
- Hippo pathway signaling and YAP/TAZ
- Gene Regulatory Network Analysis
- Glycosylation and Glycoproteins Research
- FOXO transcription factor regulation
- Histone Deacetylase Inhibitors Research
Kanazawa University
2016-2025
The University of Tokyo
2008-2020
Cell Biotech (South Korea)
2015-2019
Hiroshima University Hospital
2019
Hiroshima University
2019
Tokyo Medical University
2017
Tokyo University of Science
2007-2016
Kyoto University
2006-2016
Hokkaido University
2014
Osaka University
2013-2014
Despite the therapeutic potential of nucleic acid drugs, their clinical application has been limited in part by a lack appropriate delivery systems. Exosomes or microvesicles are small endosomally derived vesicles that secreted variety cell types and tissues. Here, we show exosomes can efficiently deliver microRNA (miRNA) to epidermal growth factor receptor (EGFR)-expressing breast cancer cells. Targeting was achieved engineering donor cells express transmembrane domain platelet-derived...
Abstract Activation of the EGFR, KRAS, and ALK oncogenes defines 3 different pathways molecular pathogenesis in lung adenocarcinoma. However, many tumors lack activation any pathway (triple-negative adenocarcinomas) posing a challenge for prognosis treatment. Here, we report an extensive genome-wide expression profiling 226 primary human stage I–II adenocarcinomas that elucidates characteristics harbor mutations or mutations, is, triple-negative adenocarcinomas. One hundred seventy-four...
Pyruvate kinase M2 (PKM2) is an alternatively spliced variant of the pyruvate gene that preferentially expressed during embryonic development and in cancer cells. PKM2 alters final rate-limiting step glycolysis, resulting cancer-specific Warburg effect (also referred to as aerobic glycolysis). Although previous reports suggest functions nonmetabolic transcriptional regulation, its significance biology remains elusive. Here we report stimulation epithelial-mesenchymal transition (EMT) results...
AbstractThe docking protein FRS2 was implicated in the transmission of extracellular signals from fibroblast growth factor (FGF) or nerve (NGF) receptors to Ras/mitogen-activated kinase signaling cascade. The two members family, FRS2α and FRS2β, are structurally very similar. Each is composed an N-terminal myristylation signal, a phosphotyrosine-binding (PTB) domain, C-terminal tail containing multiple binding sites for SH2 domains adapter Grb2 tyrosine phosphatase Shp2. Here we show that...
CRK belongs to a family of adaptor proteins that consist mostly SH2 and SH3 domains. Far Western blotting with has demonstrated it binds 135- 145-, 160-, 180-kDa proteins. The 145-kDa protein is C3G, SH3-binding guanine nucleotide exchange protein. Here, we report on the molecular cloning protein, which designated DOCK180 (180-kDa downstream CRK). isolated cDNA contains 5,598-bp open reading frame encoding an 1,866-amino-acid deduced amino acid sequence did not reveal any significant...
The docking protein FRS2 is a major downstream effector that links fibroblast growth factor (FGF) and nerve receptors with the Ras/mitogen-activated kinase signaling cascade. In this report, we demonstrate also plays pivotal role in FGF-induced recruitment activation of phosphatidylinositol 3-kinase (PI3-kinase). We tyrosine phosphorylation FRS2α leads to Grb2-mediated complex formation Gab1 its phosphorylation, resulting PI3-kinase. Furthermore, Grb2 bound tyrosine-phosphorylated through...
The docking protein FRS2α has been implicated as a mediator of signaling via fibroblast growth factor receptors (FGFRs). We have demonstrated that targeted disruption gene causes severe impairment in mouse development resulting embryonal lethality at E7.0–E7.5. Experiments with FRS2α-deficient fibroblasts demonstrate plays critical role FGF-induced mitogen-activated (MAP) kinase stimulation, phosphatidylinositol-3 (PI-3) activation, chemotactic response, and cell proliferation. Following FGF...
Abstract —The signaling cascade elicited by angiotensin II (Ang II) resembles that characteristic of growth factor stimulation, and recent evidence suggests G protein–coupled receptors transactivate to transmit mitogenic effects. In the present study, we report involvement epidermal receptor (EGF-R) in Ang II–induced extracellular signal–regulated kinase (ERK) activation, c- fos gene expression, DNA synthesis cardiac fibroblasts. induced a rapid tyrosine phosphorylation EGF-R association...
Purpose To identify stage I lung adenocarcinoma patients with a poor prognosis who will benefit from adjuvant therapy. Patients and Methods Whole gene expression profiles were obtained at 19 time points over 48-hour course human primary epithelial cells that stimulated epidermal growth factor (EGF) in the presence or absence of clinically used EGF receptor tyrosine kinase (RTK)-specific inhibitor, gefitinib. The data subjected to mathematical simulation using State Space Model (SSM)....
Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, these properties have been attributed stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms progression associated with CSCs. This study aimed identify the candidate miRNA characterise clinical significance. We established gemcitabine-resistant Panc1 cells, induced CSC-like through sphere formation. Candidate miRNAs were selected microarray analysis. The...
Abstract The aim of this study was to identify differentially-expressed miRNAs in the serum non-small cell lung cancer (NSCLC) patients that might be a clinically-useful tool for early detection. We performed miRNA expression profile analysis using TaqMan OpenArray Human panel discovery set 70 samples obtained at tumor resection and 22 non-cancer subjects (NC). Selected were then validated by quantitative PCR an independent validation from LC (n = 84) NC 23). Sixty significantly up-regulated...
Tumor recurrence is attributable to cancer stem-like cells (CSCs), the metabolic mechanisms of which currently remain obscure. Here, we uncovered critical role folate-mediated one-carbon (1C) metabolism involving mitochondrial methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and its downstream purine synthesis pathway. MTHFD2 knockdown greatly reduced tumorigenesis properties, were associated with nucleotide deficiency, caused marked accumulation 5-aminoimidazole carboxamide ribonucleotide...
Epidermal growth factor (EGF) induces tyrosine phosphorylation of the Shc adapter protein, which plays an important role in EGF-stimulated mitogenesis. stimulates Ras/mitogen-activated protein kinase (MAPK) through forming a complex with Grb2 at phosphorylated (Y) residue 317. In this study, we identified novel sites Shc, Y239 and Y240. To define pathway further, used NIH 3T3 cells expressing previously characterized mutant EGF receptor (EGF-R) lacks all known autophosphorylation but retains...
Epidermal growth factor (EGF) receptor (EGFR) can induce cell and transformation in a ligand-dependent manner. To examine whether the autophosphorylation of EGFR correlates with capacity activated to transformation, we truncated human just after residue 1011, removing all three major sites (DEL1011). Further, point mutation was introduced at another site, Tyr-992-->Phe (DEL1011+F992). The wild-type mutant receptors were stably expressed NIH 3T3 variant line that expresses an extremely low...
Breast cancer is one of the most common cancers in humans. However, our understanding cellular and molecular mechanisms underlying tumorigenesis breast tissues limited. Here, we identified a mechanism that controls ability cells to form multicellular spheroids (mammospheres). We found heregulin (HRG), ligand for ErbB3, induced mammosphere formation stem cell (BCSC)–enriched population as well lines. HRG-induced was reduced by treatment with inhibitors phosphatidyl inositol 3-kinase (PI3K) or...
Tumour-initiating cells (TICs) or cancer stem can exist as a small population in malignant tissues. The signalling pathways activated TICs that contribute to tumourigenesis are not fully understood.Several breast cell lines were sorted with CD24 and CD44, known markers for enrichment of TICs. Tumourigenesis was analysed using total RNA subjected gene expression profiling set analysis (GSEA).We showed several have CD24(-/low)/CD44(+) which may be enriched, confirmed the properties xenograft...
Inner ear mechanosensory hair cells transduce sound and balance information. Auditory emerge from a Sox2-positive sensory patch in the inner epithelium, which is progressively restricted during development. This restriction depends on action of signaling molecules. Fibroblast growth factor (FGF) signalling important specification: attenuation Fgfr1 disrupts cochlear cell formation; however, underlying mechanisms remain unknown. Here we report that absence FGFR1 signaling, expression Sox2...
The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cells. IGF2 receptor, IGF1 R, was expressed at high levels CSC-enriched populations primary Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) induced expression stemness factor, inhibitor...