- Cancer Cells and Metastasis
- TGF-β signaling in diseases
- Cell Adhesion Molecules Research
- Fibroblast Growth Factor Research
- Pancreatic and Hepatic Oncology Research
- Caveolin-1 and cellular processes
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Wnt/β-catenin signaling in development and cancer
- RNA Research and Splicing
- Signaling Pathways in Disease
- Immune cells in cancer
- Mesenchymal stem cell research
- Genetic factors in colorectal cancer
- Glycosylation and Glycoproteins Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Peptidase Inhibition and Analysis
- Neurogenesis and neuroplasticity mechanisms
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Axon Guidance and Neuronal Signaling
- Cancer Immunotherapy and Biomarkers
- Cardiac Fibrosis and Remodeling
- Occupational and environmental lung diseases
Nagoya University
2016-2025
Hiroshima University
2025
Nagoya University Hospital
2022
Tsuru University
2016
Cancer-associated fibroblasts (CAF) constitute a major component of the tumor microenvironment. Recent observations in genetically engineered mouse models and clinical studies have suggested that there may exist at least two functionally different populations CAFs, is, cancer-promoting CAFs (pCAF) cancer-restraining (rCAF). Although various pCAF markers been identified, identity rCAFs remains unknown because lack rCAF-specific marker(s). In this study, we found Meflin,...
Abstract PI3K–Akt signaling is critical for the development, progression, and metastasis of malignant tumors, but its role in tumor microenvironment has been relatively little studied. Here, we report that Akt substrate Girdin, an actin-binding protein regulates cell migration, expressed activated by phosphorylation cancer-associated fibroblasts (CAF) blood vessels within microenvironment. Lewis lung tumors grafted into mice defective Akt-mediated Girdin (SA transgenic mice) exhibited a...
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM or skeletal stem cells. Whereas MSCs have been exploited clinical medicine, the identification of MSC-specific markers has limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed cultured MSCs, fibroblasts pericytes, but not other types including epithelial, endothelial smooth muscle In vivo, Meflin by immature osteoblasts chondroblasts. addition, found on distributed...
Myofibroblasts have roles in tissue repair following damage associated with ischemia, aging, and inflammation also promote fibrosis stiffening, causing organ dysfunction. One source of myofibroblasts is mesenchymal stromal/stem cells that exist as resident fibroblasts multiple tissues. We previously identified meflin (mesenchymal stromal cell- fibroblast-expressing Linx paralogue), a glycosylphosphatidylinositol-anchored membrane protein, specific marker regulator their undifferentiated...
Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape TME toward immunosuppressive milieu and attenuate efficacy immune checkpoint blockade (ICB) therapy. However, detailed mechanism how heterogeneous regulate response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by expression Meflin, glycosylphosphatidylinositol-anchored protein marker mesenchymal stromal/stem cells, is...
Abstract Objective Owing to variations in the exterior appearances of noncancerous diseases oral cavity, clinicians may have difficulty diagnosing squamous cell carcinoma (OSCC). Tissue biopsy is confirmatory, but invasive. Therefore, reliable tumor markers for OSCC are required. Here, exosomal Alix (exoAlix) levels were measured serum/salivary samples from patients with and healthy controls (HCs). Methods Fifty‐seven admitted Nagoya University Hospital 2017 through 2019 enrolled, serum...
Abstract Background The proliferation of cancer-associated fibroblasts (CAFs) hampers drug delivery and anti-tumor immunity, inducing tumor resistance to immune checkpoint blockade (ICB) therapy. However, it has remained a challenge develop therapeutics that specifically target or modulate CAFs. Methods We investigated the involvement Meflin + cancer-restraining CAFs (rCAFs) in ICB efficacy patients with clear cell renal carcinoma (ccRCC) urothelial (UC). examined effects Am80 (a synthetic...
Human REV 7 (also known as MAD 2L2 and 2B) is involved in DNA repair, cell cycle regulation, gene transcription, carcinogenesis. In this study, we evaluated the expression of epithelial ovarian cancer ( EOC ) analyzed association between its chemosensitivity clear carcinoma CCC cells. Expression human tissues was assessed by immunohistochemical staining. detected majority s (92.0%) with especially high levels frequently observed (73.5%) compared that non‐ (53.4%). Enhanced immunoreactivity...
CD109 is a glycosylphosphatidylinositol-anchored cell surface protein that frequently detected in squamous carcinomas. negative regulator of TGF-β1 signaling human keratinocytes, and the N-terminal fragment secreted from cells after cleavage by furin protease important for modulating signaling. Previously, we found expressed glioblastoma cells; however, role not established. Here, describe effects lines. Three lines, SK-MG-1, U251MG MG178, were tested overexpression attenuated enhanced EGF...
In the progression of glioma, tumour cells often exploit perivascular microenvironment to promote their survival and resistance conventional therapies. Some these are considered be brain stem (BTSCs); however, molecular nature has not been specifically clarified because complexity glioma. Here, we identified CD109, a glycosylphosphatidylinositol-anchored protein regulator multiple signalling pathways, as critical lower-grade glioma (World Health Organization grade II/III) by...
Pathological observations show that cancer cells frequently invade the surrounding stroma in collective groups rather than through single cell migration. Here, we studied role of actin-binding protein Girdin, a specific regulator migration neuroblasts brain, We found Girdin was essential for skin line A431 on collagen gels as well their fibroblast-led invasion an organotypic culture model. provide evidence binds to β-catenin plays important roles Wnt signaling pathway and E-cadherin-mediated...
Breast cancer can be classified into several subtypes based on gene expression profiling. Basal‐like breast carcinoma (BLC) has a triple negative phenotype, that is, the subtype lacks estrogen receptor (ER), progesterone (PgR) and human epidermal growth factor 2 (HER2). It been recently reported CD109, glycosylphosphatidylinositol (GPI)‐anchored cell surface protein, is new myoepithelial marker. In present study CD109 was investigated in invasive ductal carcinomas (IDC) of...
The Sprouty (SPRY) family of proteins includes important regulators downstream signaling initiated by receptor tyrosine kinases. In the present study, we investigated role SPRY in intracellular via RET kinase activated glial cell line‐derived neurotrophic factor (GDNF). Expression SPRY1, SPRY2, SPRY3 and SPRY4 HEK293T cells transfected with GDNF α1 (GFRα1) genes significantly reduced sustained ERK activation as well ELK‐1 activation. Because expression SPRY2 was efficiently induced TGW human...
For collective invasion, cancer cells form cohesive groups comprised of leading (LCs) at the forefront and following (FCs) rear. However, molecular mechanisms that define LCs FCs remain elusive. Here, we demonstrated LCs, but not FCs, upregulated expression integrin β1 after loss intercellular adhesion. The LC-specific was posttranscriptionally regulated by TRIM27/MRTF-B complex in response to adhesion, thereby regulating stability translation mRNA via microRNA-124 LCs. Accordingly,...
Bladder cancer is one of the most common malignant diseases. Since a high-rate recurrence serious problem for early stage urothelial carcinomas, new strategies management recurrent carcinomas have been explored. CD109 glycosylphosphatidylinositol-anchored glycoprotein and expressed in various tissues, mainly squamous cell carcinomas. negatively controls transforming growth factor (TGF)-β/Smad signaling vitro. In this study, we analyzed clinical significance expression bladder using...
Malignant mesothelioma is an aggressive neoplasm for which effective treatments are lacking. We often encounter cases with a profound desmoplastic reaction, suggesting the involvement of cancer‑associated fibroblasts (CAFs) in progression. While roles CAFs have been extensively studied other tumors and led to view that cancer stroma contains heterogeneous populations CAFs, their remain unknown. previously showed connective tissue growth factor (CTGF), secreted protein, produced by both cells...