A5058509801- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Acute Myeloid Leukemia Research
- Cell death mechanisms and regulation
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
- Cancer Treatment and Pharmacology
- Lung Cancer Treatments and Mutations
- Cancer Mechanisms and Therapy
- Retinoids in leukemia and cellular processes
- Ferroptosis and cancer prognosis
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- Glycosylation and Glycoproteins Research
- Cancer Cells and Metastasis
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
Gunma University
2015-2024
Gunma Prefectural Institute of Public Health and Environmental Sciences
2020
Columbia University
2013-2018
Gunma University Hospital
2015
Tokyo Medical and Dental University
2008
Japanese Foundation For Cancer Research
2006-2007
Olympus (Japan)
2007
Japan Society of Chemotherapy
2006
Gifu Kyoritsu University
2005
The University of Tokyo
1998-2002
Monocytic leukemia zinc finger (MOZ)/KAT6A is a MOZ, Ybf2/Sas3, Sas2, Tip60 (MYST)-type histone acetyltransferase that functions as coactivator for acute myeloid 1 protein (AML1)- and Ets family transcription factor PU.1-dependent transcription. We previously reported MOZ directly interacts with p53 essential p53-dependent selective regulation of p21 expression. show here an at K120 K382 colocalizes in promyelocytic (PML) nuclear bodies following cellular stress. The MOZ–PML–p53 interaction...
Abstract Epigenetic programs are dysregulated in acute myeloid leukemia (AML) and help enforce an oncogenic state of differentiation arrest. To identify key epigenetic regulators AML cell fate, we performed a differentiation-focused CRISPR screen cells. This identified the histone acetyltransferase KAT6A as novel regulator that drives critical leukemogenic gene-expression programs. We show is initiator newly described transcriptional control module which KAT6A-catalyzed promoter H3K9ac bound...
The oncogene Akt/PKB/RAC-PK is a serine/threonine kinase that mediates survival signals and has protective effects against apoptosis induced by variety of stimuli. activity Akt been demonstrated to be critical in transmitting signals. We found protein was down-regulated during apoptosis. down-regulation blocked caspase inhibitor, indicating cleaved caspases incubation with active vitro revealed it at three sites produce 40- 44-kDa fragments. two cleavage were between the NH2-terminal...
Chemotherapeutic drugs exhibit their cytotoxic effect by inducing apoptosis in tumor cells. Because the serine/threonine kinase Akt is involved suppression, we investigated relationship between activity and drug sensitivity. We discovered that certain chemotherapeutic induced with caspase activation only when was inactivated after treatment, while inactivation of not observed cells showed resistance to drug-induced activation. So, turn-off Akt-mediated survival signal correlated sensitivity...
Significance The N-terminally truncated isoform of p63 (ΔNp63) is overexpressed in some forms squamous cell carcinoma (SCC). Here we show that the anaphase-promoting complex/cyclosome (APC/C) degradation machinery plays an essential role regulating proteolysis ΔNp63. We report as well syntaxin-binding protein 4 (Stxbp4) suppresses APC/C-mediated ubiquitination and ΔNp63 thereby drives oncogenic potential SCC. Aberrancies this newly defined mechanism could account for overexpression These...
Cancer-associated fibroblasts (CAFs) play vital roles in tumor progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and immunosuppression. In the present study, we sought to identify key regulators of pro-tumoral functions CAFs head neck squamous cell carcinoma (HNSCC). mRNA expression data obtained from The Cancer Genome Atlas revealed that CAF-specific correlated with genes relate an immunosuppressive microenvironment a HNSCC cohort. RNA sequencing normal isolated...
Background and Objectives The Caspase14 (CASP14) was reported that the low expression of CASP14 in ovarian cancer colon associated with progression, on other hand, breast higher than non‐cancerous tissues. purpose this study is to determine clinical significance cancer. Methods We performed immunohistochemistry for CASP14, ER, PgR, HER2, Ki67, EGFR, CK5/6, CD44, CD24, ALDH1, claudins, androgen receptor 222 patients including 55 TNBC cases, evaluated relationship above‐mentioned markers,...
Allergic asthma and allergic dermatitis are chronic inflammatory diseases characterized by an accumulation of eosinophils at sites inflammation. Eotaxin-1/CCL11 eotaxin-3/CCL26 members the CC chemokine family, which known to be potent chemoattractants for eosinophils. We observed that a human lung fibroblast, HFL-1 produces eotaxin-1 -3 in response TNF-α plus IL-4 stimulation, accompanied with NF-κB STAT6 activation. explored signaling pathways operative production using several inhibitors....
Purpose: Expression of the ΔN isoform p63 (ΔNp63) is a diagnostic marker highly specific for lung squamous cell carcinoma (SCC). We previously found that Syntaxin Binding Protein 4 (STXBP4) regulates ΔNp63 ubiquitination, suggesting STXBP4 may also be an SCC biomarker. To address this issue, we investigated role expression in biology and impact on prognosis.Experimental Design: carried out clinicopathologic analysis 87 patients. Whole transcriptome using RNA-seq was performed STXBP4-positive...
NSC697923, a ubiquitin-conjugating enzyme E2 (UBE2) inhibitor, was suggested as an agent to degrade hypoxia-inducible factor 1 alpha subunit (HIF1α), key in radiation resistance. We attempted clarify whether NSC697923 could overcome resistance.Radiation resistance and expression of HIFs were evaluated radiation-sensitive HCT116 -resistant SW480 cells treated with or without under normoxia hypoxia vitro vivo. examined NSC697923-regulated genes using RNA sequencing.HIF significantly increased...
The identification of genes with synthetic lethality in the context mutant TP53 is a promising strategy for treatment basal-like triple negative breast cancer (TNBC). This study investigated regulators (R248Q) TNBC and their impact on tumorigenesis.TNBC cells were analyzed by RNA-seq, synthetic-lethal shRNA knock-down screening, to identify related expression TP53. A tissue microarray 232 samples, that included 66 cases, was used assess clinicopathological correlates tumor protein...
CD13/aminopeptidase‐N (CD13/APN) is an important regulator of angiogenesis where its expression on activated blood vessels induced by angiogenic signals. A previous study demonstrated that suppressed under the presence high concentrations aminopeptidase antagonists. However, mechanisms underlying inhibition morphogenesis antagonists have not been elucidated. In this study, we for first time examined effects continuous treatment therapeutic dose vascular endothelial capillary‐like tube...
This study aims to explore the expression level of ΔNp63 in esophageal squamous cell carcinoma ( ESCC ). To investigate association between (p40) and biology, we compared levels normal tumor tissues, with a specific focus on diagnostic value . We analyzed 160 consecutive patients who underwent surgical resection without neoadjuvant chemotherapy at Gunma University Hospital (Maebashi, Japan) September 2000 January 2010. The clinicopathological characteristics survival were subclassified based...
Abstract Background Lung squamous cell carcinoma (LSCC) remains a challenging disease to treat, and further improvements in prognosis are dependent upon the identification of LSCC-specific therapeutic biomarkers and/or targets. We previously found that Syntaxin Binding Protein 4 (STXBP4) plays crucial role lesion growth and, therefore, clinical outcomes LSCC patients through regulation tumor protein p63 (TP63) ubiquitination. Methods To clarify impact STXBP4 TP63 for therapeutics, we...
Zinc deficiency has been linked to human diseases, including cancer. MDMX, a crucial zinc-containing negative regulator of p53, found be amplified or overexpressed in various cancers and implicated the cancer initiation progression. We report here that zinc depletion by ion chelator TPEN Chelex resin results MDMX protein degradation ubiquitination-independent 20S proteasome-dependent manner. Restoration led recovery cellular levels MDMX. Further, treatment inhibits growth MCF-7 breast cell...
Abstract The phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway plays a vital role in cell proliferation, apoptosis, metabolism, and angiogenesis various human cancers, including head neck squamous carcinoma (HNSCC). In the present study, we aimed to clarify AKT, which is major downstream effector PI3K‐AKT‐mTOR pathway, HNSCC. We first investigated mRNA expression AKT isoforms using RNA‐sequencing data from Cancer Genome Atlas database. observed specific...
Thymic epithelial tumors (TETs) comprise several histologies of thymoma and thymic carcinomas (TCs), TC frequently metastasizes causes death. We therefore aimed here to identify key molecules closely related prognosis their biological roles in high-risk TETs, particularly TCs.RNA sequence analysis demonstrated that hypoxia-related genes were highly expressed TETs. The expression the gene CA9 was noteworthy, TCs. Immunohistochemical revealed 81.0% TCs 20.7% all TET samples. significantly...