ArticlePloS one2015
Human TM9SF4 Is a New Gene Down-Regulated by Hypoxia and Involved in Cell Adhesion of Leukemic Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- Mapping the genetic landscape of suicide risk: Insights from genomic SEM.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- A genome-wide association study of neonatal metabolites.Cell genomics · 2024Article
- Prognostic analysis of patients with gastric cancer based on NFrontiers in pharmacology · 2024Article
- TM9SF1 offers utility as an efficient predictor of clinical severity and mortality among acute respiratory distress syndrome patients.Frontiers in immunology · 2024Article
- A Golgi-Located Transmembrane Nine Protein Gene TMN11 Functions in Manganese/Cadmium Homeostasis and Regulates Growth and Seed Development in Rice.International journal of molecular sciences · 2022Article
- TM9SF1 knockdown decreases inflammation by enhancing autophagy in a mouse model of acute lung injury.Heliyon · 2022Article
- Golgi-localized membrane protein AtTMN1/EMP12 functions in the deposition of rhamnogalacturonan II and I for cell growth in Arabidopsis.Journal of experimental botany · 2021Article
- TM9SF4 expression in tumor tissues: a novel diagnostic biomarker for gastrointestinal tumors.Translational cancer research · 2020Article
- Human NK cell receptor KIR2DS4 detects a conserved bacterial epitope presented by HLA-C.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- TM9SF4 is a novel factor promoting autophagic flux under amino acid starvation.Cell death and differentiation · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe transmembrane 9 superfamily protein member 4, TM9SF4, belongs to the TM9SF family of proteins highly conserved through evolution. TM9SF4 homologs, previously identified in many different species, were mainly involved in cellular adhesion, innate immunity and phagocytosis. In human, the function and biological significance of TM9SF4 are currently under investigation. However, TM9SF4 was found overexpressed in human metastatic melanoma and in a small subset of acute myeloid leukemia (AMLs) and myelodysplastic syndromes, consistent with an oncogenic function of this gene. PURPOSE AND
resultsIn this study, we first analyzed the expression and regulation of TM9SF4 in normal and leukemic cells and identified TM9SF4 as a gene highly expressed in human quiescent CD34+ hematopoietic progenitor cells (HPCs), regulated during monocytic and granulocytic differentiation of HPCs, both lineages giving rise to mature myeloid cells involved in adhesion, phagocytosis and immunity. Then, we found that TM9SF4 is markedly overexpressed in leukemic cells and in AMLs, particularly in M2, M3 and M4 AMLs (i.e., in AMLs characterized by the presence of a more or less differentiated granulocytic progeny), as compared to normal CD34+ HPCs. Proliferation and differentiation of HPCs occurs in hypoxia, a physiological condition in bone marrow, but also a crucial component of cancer microenvironment. Here, we investigated the impact of hypoxia on TM9SF4 expression in leukemic cells and identified TM9SF4 as a direct target of HIF-1α, downregulated in these cells by hypoxia. Then, we found that the hypoxia-mediated downregulation of TM9SF4 expression is associated with a decrease of cell adhesion of leukemic cells to fibronectin, thus demonstrating that human TM9SF4 is a new molecule involved in leukemic cell adhesion.
conclusionsAltogether, our study reports for the first time the expression of TM9SF4 at the level of normal and leukemic hematopoietic cells and its marked expression at the level of AMLs displaying granulocytic differentiation.
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