A5072302253- Cancer-related gene regulation
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Folate and B Vitamins Research
- Amino Acid Enzymes and Metabolism
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sperm and Testicular Function
- Heme Oxygenase-1 and Carbon Monoxide
- Protease and Inhibitor Mechanisms
- Calcium signaling and nucleotide metabolism
- Adenosine and Purinergic Signaling
- Mitochondrial Function and Pathology
- Cancer Cells and Metastasis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Blood Coagulation and Thrombosis Mechanisms
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Neonatal Health and Biochemistry
- BRCA gene mutations in cancer
- Advanced Breast Cancer Therapies
- Sphingolipid Metabolism and Signaling
- Ubiquitin and proteasome pathways
Tokyo Medical University
2018-2024
Keio University
2008-2024
John Wiley & Sons (United Kingdom)
2019
Hudson Institute
2019
Johns Hopkins Medicine
2013-2014
Johns Hopkins University
2012-2014
Institute of Cell Biology
2014
Hokkaido University
2004-2013
Japan Science and Technology Agency
2012
Nagoya University
2008
Significance Cancer cells release from their cell surface membrane-lined microvesicles (MVs), which contain proteins, mRNAs, and microRNAs that can be taken up by other cells. We report breast cancer exposed to decreased oxygen availability (hypoxia) increase production of MVs, stimulate invasion metastasis recipient Increased MV shedding hypoxic requires expression hypoxia-inducible factors (HIFs), activate transcription the RAB22A gene, small GTPase RAB22A, is a protein localizes budding...
Haem oxygenase (HO)-1/carbon monoxide (CO) protects cancer cells from oxidative stress, but the gas-responsive signalling mechanisms remain unknown. Here we show using metabolomics that CO-sensitive methylation of PFKFB3, an enzyme producing fructose 2,6-bisphosphate (F-2,6-BP), serves as a switch to activate phosphofructokinase-1, rate-limiting glycolytic enzyme. In human leukaemia U937 cells, PFKFB3 is asymmetrically di-methylated at R131 and R134 through modification by protein arginine...
Metastasis involves critical interactions between cancer and stromal cells. Intratumoral hypoxia promotes metastasis through activation of hypoxia-inducible factors (HIFs). We demonstrate that HIFs mediate paracrine signaling breast cells (BCCs) mesenchymal stem (MSCs) to promote metastasis. In a mouse orthotopic implantation model, MSCs were recruited primary tumors promoted BCC LNs lungs in HIF-dependent manner. Coculture with BCCs augmented HIF activity BCCs. Additionally, coculture...
Significance The recruitment of host stromal cells, such as macrophages and mesenchymal stem cells (MSCs), to the primary tumor is a critical step toward cancer malignancy. We have identified signals that are exchanged between breast (BCCs) MSCs. This signaling increases both MSCs tumors metastasis BCCs lymph nodes lungs. Reduced oxygen levels (hypoxia) in cancers associated with increased risk decreased patient survival. show hypoxia stimulates due activity hypoxia-inducible factors (HIFs)....
Cancer cells re-program their metabolic machinery to meet the requirements of malignant transformation and progression. Glutaminase 1 (GLS1) was traditionally known as a mitochondrial enzyme that hydrolyzes glutamine into glutamate fuels rapid proliferation cancer cells. However, emerging evidence has now revealed GLS1 might be novel oncogene involved in tumorigenesis progression human cancers. In this study, we sought determine whether implicated invasion metastasis colorectal carcinoma,...
// Lisha Xiang 1,2,3 , Daniele M. Gilkes 2,3 Hongxia Hu Naoharu Takano 2,3,5 Weibo Luo Haiquan Lu John W. Bullen Debangshu Samanta Houjie Liang 1 and Gregg L. Semenza 2,3,4 Department of Oncology Southwest Cancer Center, Hospital, Third Military Medical University, Chongqing, China 2 Vascular Program, Institute for Cell Engineering, Johns Hopkins University School Medicine, Baltimore, MD 3 McKusick-Nathans Genetic 4 Departments Pediatrics, Oncology, Radiation Biological Chemistry, 5...
Abstract Triple-negative breast cancer (TNBC) chemoresistance hampers the ability to effectively treat patients. Identification of mechanisms driving can lead strategies improve treatment. Here, we revealed that protein arginine methyltransferase-1 (PRMT1) simultaneously methylates D-3-phosphoglycerate dehydrogenase (PHGDH), a critical enzyme in serine synthesis, and glycolytic enzymes PFKFB3 PKM2 TNBC cells. 13C metabolic flux analyses showed PRMT1-dependent methylation these three diverts...
Carbon monoxide (CO) is a stress-inducible gas generated by heme oxygenase (HO) eliciting adaptive responses against toxicants; however, mechanisms for its reception remain unknown. Serendipitous observation in metabolome analysis CO-overproducing livers suggested roles of cystathionine beta-synthase (CBS) that rate-limits transsulfuration pathway and H(2)S generation, the gas-responsive receptor. Studies using recombinant CBS indicated CO binds to prosthetic heme, stabilizing 6-coordinated...
// Hongxia Hu 1,2,3 , Naoharu Takano 2,3 Lisha Xiang 2,3,4 Daniele M. Gilkes Weibo Luo 2,3,5 and Gregg L. Semenza 2,3,5,6 1 Predoctoral Training Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 2 McKusick-Nathans Institute Genetic 3 Vascular Program, for Cell Engineering, 4 Department Oncology Southwest Cancer Center, Hospital, Third Military Medical University, Chongqing, China 5 Biological Chemistry, 6 Departments Oncology, Pediatrics, Radiation...
Abstract In the cell cycle, G 1 /S transition is controlled by cyclin‐dependent kinase (CDK) 4/6‐cyclin D complex. Constitutive activation of CDK4/6 dysregulates transition, leading to oncogenic transformation. We found that 3 inhibitors, abemaciclib, ribociclib, and palbociclib, exerted a cytocidal effect as well cytostatic at phase in cancer lines, including A549 human non–small lung cells. Among these abemaciclib exhibited most potent cytotoxic effect. The cell‐death phenotype induced...
Identification of the hydrolytic enzymes involved in follicle rupture during vertebrate ovulation remains a central challenge for research reproductive biology. Here, we report previously uncharacterized approach to this problem by using an vitro system medaka, Oryzias latipes , which is small freshwater teleost. We found that medaka ovary involves cooperation at least three matrix metalloproteinases (MMPs), together with tissue inhibitor metalloproteinase-2b protein. determined discrete...
Abstract Cystathionine β-synthase (CBS) catalyzes metabolic reactions that convert homocysteine to cystathionine. To assess the role of CBS in human glioma, cells were stably transfected with lentiviral vectors encoding shRNA targeting or a nontargeting control shRNA, and subclones injected into immunodeficient mice. Interestingly, decreased expression did not affect proliferation vitro but latency period before rapid tumor xenograft growth after subcutaneous injection increased incidence...
Abstract Background Autophagy plays an important role in tumour cell growth and survival also promotes resistance to chemotherapy. Hence, autophagy has been targeted for cancer therapy. We previously reported that macrolide antibiotics including azithromycin (AZM) inhibit various types of cells vitro. However, the underlying molecular mechanism inhibition remains unclear. Here, we aimed identify target AZM inhibiting autophagy. Methods identified AZM-binding proteins using AZM-conjugated...
Abstract Cancer cells use autophagy for growth, survival, and cytoprotection from chemotherapy. Therefore, inhibitors appear to be good candidates cancer treatment. Our group previously reported that macrolide antibiotics, especially azithromycin (AZM), have potent inhibitory effects, combination treatment with tyrosine kinase or proteasome enhances their anti–cancer activity. In this study, we evaluated the effect of therapy DNA‐damaging drugs AZM in non–small‐cell lung (NSCLC) cells. We...
IL-6 has manifold biologic functions in immune and inflammatory responses is produced by a variety type of cells. In this work, we used the whole blood culture to identify cells expressing gene/protein after various stimulation. When was incubated with LPS or Con A, much activity, measured growth promoting assay using murine IL-6-dependent hybridoma clone, detected plasma as early 4 h continued increase time, reaching plateau around 12 h. Immunocytochemical analysis anti-rIL-6 antiserum...
Tyrosine kinase inhibitors (TKIs) induce autophagy in many types of cancer cells. We previously reported that gefitinib (GEF) and imatinib (IMA) epidermal growth factor receptor (EGFR) knock-out A549 non-BCR-ABL-expressing leukemia cell lines, respectively. This evidence suggests TKI-induced is independent the original target molecules. The present study compared autophagy-inducing abilities various TKIs, regardless their targets, by quantitative flux assay. established stable clones...
Human kallikrein 8 ( KLK8 ) is a member of the human gene family serine proteases, and its protein, hK8, has recently been suggested to serve as new ovarian cancer marker. To gain insights into physiological role active recombinant enzyme was obtained in pure state for biochemical enzymatic characterizations. hK8 had trypsin‐like activity with strong preference Arg over Lys P1 position, inhibited by typical protease inhibitors. The degraded casein, fibronectin, gelatin, collagen type IV,...
Increased catalytic activity of CBS (cystathionine β-synthase) was recently shown to mediate vasodilation the cerebral microcirculation, which is initiated within minutes onset acute hypoxia. To test whether chronic hypoxia a stimulus for increased expression, U87-MG human glioblastoma and PC12 rat phaeochromocytoma cells were exposed 1% or 20% O2 24–72 h. mRNA protein expression in hypoxic cells. Hypoxic induction abrogated transfected with vector encoding shRNA targeting HIF...
Lysosomes are single-membraned organelles that mediate the intracellular degradation of macromolecules. Various stress can induce lysosomal membrane permeabilization (LMP), translocating intralysosomal components, such as cathepsins, to cytoplasm, which induces lysosomal-dependent cell death (LDCD). This study reports p53 regulates LMP in response DNA-damaging drugs. Treating wild-type TP53 A549 cells with drugs (namely, doxorubicin, carboplatin, and etoposide) induced accelerated more...
TP53 mutation is one of the most frequent gene mutations in head and neck squamous cell carcinoma (HNSCC) could be a potential therapeutic target. Recently, WEE1 G2 checkpoint kinase (WEE1) inhibitor adavosertib (Adv) has attracted attention because its selective cytotoxicity against TP53‑mutated cells shown promising activity early phase clinical trials. In present study, it was demonstrated that combined treatment with Adv histone deacetylase 6 (HDAC6) inhibitor, ricolinostat (RCS),...
Although carbon monoxide derived from heme oxygenase has been reported to exert diverse biological actions in mammals, macromolecules responsible for its direct reception and functional outcomes of the gas binding remain largely unknown. Based on our previous results vivo suggesting serves as an inhibitor cystathionine β-synthase that rate-limits transsulfuration pathway generation hydrogen sulfide, we have herein hypothesized might serve a regulator protein methylation through accelerating...