Motoharu Seiki

Motoharu Seiki

Ph.D.

About

530
Publications
32,217
Reads
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40,821
Citations
Introduction
Motoharu Seiki currently works at Kanazawa University. Motoharu does research in Cell Biology. Their current project is 'HCC and MT1-MMP.'
Additional affiliations
July 2015 - March 2019
Kanazawa University
Position
  • Professor
April 2013 - June 2015
Kochi University
Position
  • Specially Appointed Professor (Full)
January 1997 - December 2013
The University of Tokyo
Position
  • Professor (Full)

Publications

Publications (530)
Article
Full-text available
Background: To evaluate whether urine laminin-γ2 monomer (Ln-γ2m) offers a useful biomarker for patients with non-muscle-invasive bladder cancer (NMIBC). Methods: Participants comprised 297 patients, including 111 patients with NMIBC, 136 patients with benign genitourinary disease (BD) and 50 healthy donors (HD). Urine Ln-γ2m was prospectively m...
Article
Full-text available
To develop effective therapeutics against COVID-19, it is necessary to elucidate in detail the infection mechanism of the causative agent, SARS-CoV-2. SARS-CoV-2 binds to the cell surface receptor ACE2 via the spike protein, and then the spike protein is cleaved by host proteases to enable entry.
Preprint
Full-text available
The ongoing global vaccination program to prevent SARS-CoV-2 infection, the causative agent of COVID-19, has had significant success. However, recently virus variants have emerged that can evade the immunity in a host achieved through vaccination. Consequently, new therapeutic agents that can efficiently prevent infection from these new variants, a...
Article
Full-text available
Laminins are heterotrimeric extracellular matrix proteins composed of α, β, and γ chains. The γ2 chain (Lm-γ2) is a frequently expressed monomer and its expression is closely associated with cancer progression. Lm-γ2 contains an EGF-like domain in its domain III (DIII or LEb). Matrix metalloproteinases (MMPs) can cleave off the DIII region of Lm-γ2...
Article
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Hypoxia-inducible factor-1 (HIF-1) plays essential roles in human diseases, though its central role in oxygen homoeostasis hinders the development of direct HIF-1-targeted pharmacological approaches. Here, we surveyed small-molecule compounds that efficiently inhibit the transcriptional activity of HIF-1 without affecting body homoeostasis. We focu...
Article
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Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which m...
Preprint
Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which m...
Article
Full-text available
Listeria monocytogenes (LM) infection induces pyroptosis, a form of regulated necrosis, in host macrophages via inflammasome activation. Here, we examined the role of Mint3 in macrophages, which promotes glycolysis via hypoxia-inducible factor-1 activation, during the initiation of pyroptosis following LM infection. Our results showed that Mint3-de...
Article
Backgrounds and aims: Structural dynamics of basement membrane components remained to be elucidated in the process of hepatocarcinogenesis. We evaluated the characteristics of hepatocellular carcinoma (HCC) expressing laminin γ2 monomer (LG2m), a previously unrecognized basement membrane component not detected in normal tissues, for HCC diagnosis....
Article
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Munc-18 interacting protein 3 (Mint3) is an activator of hypoxia-inducible factor-1 in cancer cells, macrophages, and cancer-associated fibroblasts under pathological conditions. However, exactly which cells highly express Mint3 in vivo and whether Mint3 depletion affects their physiological functions remain unclear. Here, we surveyed mouse tissues...
Article
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Cellular migration, coupled with the degradation of the extracellular matrix (ECM), is a key step in tumor invasion and represents a promising therapeutic target in malignant tumors. Focal adhesions (FAs) and invadopodia, which are distinct actin-based cellular structures, play key roles in cellular migration and ECM degradation, respectively. The...
Article
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Pancreatic cancer is one of the most fatal cancers without druggable molecular targets. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcriptional factor that promotes malignancy in various cancers including pancreatic cancer. Herein, we found that HIF-1 is accumulated in normoxic or moderate hypoxic areas of pancreatic cancer xenografts...
Article
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Cancer cells adapt to various stress conditions by optimizing gene expression profiles via transcriptional and translational regulation. However, whether and how EXOSC9, a component of the RNA exosome complex, regulates adaptation to stress conditions and tumorigenicity in cancer cells remain unclear. Here, we examined the effects of EXOSC9 depleti...
Article
We developed a modified invasion assay in three‐dimensional (3D) gels that permits isolation of invading cells as living cells, termed an invading cell–trapping (iCT) assay. A small cell strainer consisting of nylon mesh with pores of 40‐µm square is used in this assay. A layer of gel composed of extracellular‐matrix components is formed on each si...
Article
Full-text available
Formation of intrahepatic bile ducts (IHBDs) proceeds in accordance with their microenvironment. Particularly, mesenchymal cells around portal veins regulate the differentiation and ductular morphogenesis of cholangiocytes in the developing liver; however, further studies are needed to fully understand the arrangement of IHBDs into a continuous hie...
Article
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Pathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood flow and splitting of pre-existing capillaries. In this report, mice lacking the protease MT1-MMP...
Article
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Background: Interaction between cancer cells and fibroblasts mediated by extracellular matrix metalloproteinase inducer (emmprin, CD147) is important in the invasion and proliferation of cancer cells. However, the exact mechanism of emmprin mediated stimulation of matrix metalloprotease-2 (MMP-2) production from fibroblasts has not been elucidated...
Article
Full-text available
Laminin (Ln)-332 consists of α3, β3, and γ2 chains, which mediate epithelial cell adhesion to the basement membrane. Ln-γ2, a component of Ln-332, is frequently expressed as a monomer in the invasion front of several types of malignant tissues without simultaneous expression of Ln-α3 and/or Ln-β3 chains. Moreover, monomeric Ln-γ2 induces tumor cell...
Article
Full-text available
A modified invasion assay using a three-dimensional collagen gel was developed that enables isolation of invasive living cells; it was named the invading cell trapping (iCT) assay. A small cell strainer consisting of a nylon mesh with 40-μm2 pores was used, and collagen gel layers formed across the membrane. Test cells were seeded in the lower gel...
Article
Full-text available
Matrix metalloproteinases are involved in vascular remodeling. Little is known about their immune regulatory role in atherosclerosis. Here we show that mice deficient for MT4-MMP have increased adherence of macrophages to inflamed peritonea, and larger lipid deposits and macrophage burden in atherosclerotic plaques. We also demonstrate that MT4-MMP...
Chapter
Proteolytic cleavage of membrane proteins can alter their functions depending on the cleavage sites. We recently demonstrated that membrane type 1 matrix metalloproteinase (MT1-MMP ) converts the tumor suppressor EphA2 into an oncogenic signal transducer through EphA2 cleavage. The cleaved EphA2 fragment that remains at the cell surface may be a be...
Article
Full-text available
Because membrane type 1-matrix metalloproteinase 1 (MT1-MMP) and erythropoietin-producing hepatocellular receptor 2 (EphA2) expression are upregulated by the Ras/mitogen-activated protein kinase pathway, they are frequently coexpressed in malignant tumors. MT1-MMP cleaves the N-terminal ligand-binding domain of EphA2 and inactivates its ligand-depe...
Article
Full-text available
Background Monomeric laminin-γ2 in urine is a potential biomarker for bladder cancer. However, the current detection system uses an antibody that cannot discriminate between monomeric laminin-γ2 and the heterotrimeric γ2 chain of laminin-332, which may cause false-positive reactions. The present study aimed to develop a fully automated chemilumines...
Article
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Matrix metalloproteinases (MMPs) constitute a large group of endoproteases that play important functions during embryonic development, tumor metastasis and angiogenesis by degrading components of the extracellular matrix. Within this family, we focused our study on Mt4-mmp (also called Mmp17) that belongs to a distinct subset that is anchored to th...
Data
Database containing quantified data from real-time PCR and western blot analysis (in Fig 4) and ventral neural tube patterning (in S2 Fig). (XLSX)
Data
Mt4-mmp is not expressed in the proepicardium and epicardium at early developmental stages. (A-B) LacZ staining of sagital sections from E9.5 Mt4-mmpLacZ/+ embryos illustrating the lack of βgal-positive cells in the region of the proepicardium. (C-H) Double labelling immunohistochemistry for anti-WT-1 (arrows in red) and anti-βgal (green). No doubl...
Data
Ventral patterning and specification of the embryonic neural tube. (A-C) Double-labelling immunohistochemistry for the transcription factors Nkx6.1 (red) and Olig2 (green) in the neural tube of E10.5 WT, HT and KO embryos. (D-F) Immunostaining for FoxA2 (red) demonstrated that the floor plate is properly specified in the WT, HT and KO neural tubes....
Article
Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes...
Article
Imiquimod is an imidazoquinoline immune response modifier that is used in antiviral and antial-lergic creams. Combination therapy using transcutaneous imiquimod and oral sorafenib was previously demonstrated to reduce the tumor burden of renal cell carcinoma growing cutaneously in a mouse model. In the present study, an orthotopic mouse model was u...
Article
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Cancer metastasis is intricately orchestrated by both cancer and normal cells, such as endothelial cells and macrophages. Monocytes/macrophages, which are often co-opted by cancer cells and promote tumor malignancy, acquire more than half of their energy from glycolysis even during normoxic conditions. This glycolytic activity is maintained during...
Article
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Fibroblasts are some of the major cells in tumour tissues that influence tumour progression and drug resistance. However, our understanding on fibroblast-mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3 (Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even during normoxia in cancer cells, macrophag...
Article
Full-text available
The diagnosis of hepatocellular carcinoma (HCC) in the early stages is important for successful clinical management. Laminin (Ln)-γ2 expression has been reported in various types of malignant carcinomas. We recently developed a highly sensitive method to measure serum monomeric Ln-γ2 levels using a fully automated chemiluminescent immunoassay (CLIA...
Article
Full-text available
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed in different types of invasive and proliferative cells, including cancer cells and stromal cells. MT1-MMP cleaves extracellular matrix proteins, membrane proteins, and other pericellular proteins, thereby changing the cellular microenvironment and regulating signal activation. Critical...
Article
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Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by...
Article
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Type I IFNs (IFN-α/β) play crucial roles in the elimination of invading viruses. Multiple immune cells including macrophages recognize viral infection through a variety of pattern recognition receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate type I IFN secretion and subsequent anti...
Article
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Loss of anchorage to the extracellular matrix leads to apoptosis (anoikis) in normal cells, but cancerous cells are usually resistant to such stress. Here we report the pivotal role of an E3 ubiquitin ligase, ring-finger protein 126 (RNF126), in the resistance of cancer cells to the stress associated with non-adherent conditions. Non-adherent cance...
Article
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Exosomes are extracellular vesicles that influence cellular behavior and enhance cancer aggressiveness by carrying bioactive molecules. The mechanisms that regulate exosome secretion are poorly understood. Here, we show that the actin cytoskeletal regulatory protein cortactin promotes exosome secretion. Knockdown or overexpression of cortactin in c...
Article
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Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develo...
Data
Glycogen staining in mammary gland tissues from Mmp14 (+∕ −) and Mmp14 (−∕ −) mice The mammary gland tissues sections from Mmp14 (+∕ −; heterozygote) and Mmp14 (−∕ −) mice were stained with Alexa Fluor 594 conjugated GSA-II. Nuclei were visualized with DAPI. Scale bar = 50 µm.
Data
Glycogen staining in liver tissues from Mmp14 (+∕ +) and Mmp14 (−∕ −) mice The liver tissues sections from Mmp14 (+∕ +) and Mmp14 (−∕ −) mice were stained with Alexa Fluor 594 conjugated GSA-II. Nuclei were visualized with DAPI. Scale bar = 100 µm.
Data
Silencing Mmp14 enlarged lysosomes in mammary epithelial cells Images are showing EpH4 cells transduced with RAB7 tagged with m-cherry (A) without- or (B) with- silencing Mmp14.
Data
Mmp14 (−∕ −) has less lipid volume and high stromal cell density LS-TAFI 3D images (Mori et al. 2012) are showing the whole mount mammary glands from (a) Mmp14 (+∕ +) and (b) Mmp14 (−∕ −) mice. Scale bar = 50 µm. (c) Lipid volume and (d) stromal cell density were calculated from a scanned volume and cell volume measured from (a) and (b). Image proc...
Data
List of lipids (non-comprehensive) detected in mammary gland extracts by LC-MS/MS. Each identified lipid was detected with m∕z less than 10 ppm difference from the expected theoretical mass of the lipid with adduct TG = triglyceride/SM = sphingomyelin/PC = phosphatidylcholine/lysoPC = lysophosphatidylcholine/PI = phosphoinositol Note: Lipid notatio...
Data
Electron microscopic images of Mmp14 (+∕ +) and Mmp14 (−∕ −) mammary epithelial cells Images are showing higher magnification of images on Fig. 4a (Mmp14 (+∕ +)) and 4b (Mmp14 (−∕ −)). Arrows indicate: early endosome (green), late endosome (blue), lysosome (purple), autophagophore (yellow), autophagosome (orange) and autolysosome (red). Scale bar =...
Data
Morphological recognition of endocytic and autophagic organelles The definitions of vesicles observed in ultrastructural analyses are summarized. Endocytic organelles (early endosome, late endosome and lysosome) and autophagic organelles (autophagophore, autophagosome and autolysosome) are indicated as ultrastructural images captured in analyses an...
Article
Full-text available
Unlike most cells, cancer cells activate hypoxia inducible factor-1 (HIF-1) to use glycolysis even at normal oxygen levels, or normoxia. Therefore, HIF-1 is an attractive target in cancer therapy. However, the regulation of HIF-1 during normoxia is not well characterised, although Mint3 was recently found to activate HIF-1 in cancer cells and macro...