Laminin-5 (LN5) is a matrix component of epithelial tissue basement membranes and plays an important role in the initiation and maintenance of epithelial cell anchorage to the underlying connective tissue. Here we show that two distinct LN5 function-inhibitory antibodies, both of which bind the globular domain of the alpha3 subunit, inhibit proliferation of epithelial cells. These same antibodies also induce a decrease in mitogen-activated protein kinase activity. Inhibition of proliferation by the function-perturbing LN5 antibodies is reversed upon removal of the antibodies and can be overcome by providing the antibody-treated cells with exogenous LN5 and rat tail collagen. Because epithelial cells use the integrin receptor alpha3beta1 to interact with both LN5 and rat tail collagen, we next investigated the possibility that integrin alpha3beta1 is involved in mediating the proliferative impact of LN5. Proliferation of human epithelial cells is significantly inhibited by a function-perturbing alpha3 integrin antibody. In addition, antibody activation of beta1 integrin restores the proliferation of epithelial cells treated with LN5 function-perturbing antibodies. These data indicate that a complex comprising LN5 and alpha3beta1 integrin is multifunctional and contributes not only to epithelial cell adhesion but also to the regulation of cell growth via a signaling pathway involving mitogen-activated protein kinase. We discuss our study in light of recent evidence that LN5 expression is up-regulated at the leading tips of tumors, where it may play a role in tumor cell proliferation.
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http://dx.doi.org/10.1091/mbc.10.2.259 | DOI Listing |
An Acad Bras Cienc
January 2025
Universidade Federal de Pernambuco, Departamento de Histologia e Embriologia, Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50760-420 Recife, PE, Brazil.
Matrix metalloproteinases (MMP) have been identified as biomarkers for several diseases, including cancer. The increase in the expression of these enzymes has been related to greater tumor aggressiveness. MMP-26 is expressed constitutively in the endometrium and some cancer cells of epithelial origin.
View Article and Find Full Text PDFJ Appl Oral Sci
January 2025
Ningde Hospital Affiliated to Ningde Normal University, Department of Stomatology, Fujian, China.
Objective: This study aimed to investigate the role of transmembrane emp24 domain-containing protein 2 (TMED2) in oral squamous cell carcinoma (OSCC).
Methodology: A bioinformatics analysis was first conducted to explore TMED2 expression in OSCC and its relation with overall survival. The analysis results were further verified by assessing TMED2 expression levels in human normal oral keratinocyte cells and human OSCC cell lines using quantitative real-time polymerase chain reaction and the Western blot.
Sci Adv
January 2025
Division of Molecular Medicine, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Ketogenesis is a dynamic metabolic conduit supporting hepatic fat oxidation particularly when carbohydrates are in short supply. Ketone bodies may be recycled into anabolic substrates, but a physiological role for this process has not been identified. Here, we use mass spectrometry-based C-isotope tracing and shotgun lipidomics to establish a link between hepatic ketogenesis and lipid anabolism.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA.
Programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) interactions are targets for immunotherapies aimed to reinvigorate T cell function. Recently, it was documented that PD-L1 regulates dendritic cell (DC) migration through intracellular signaling events. In this study, we find that both preclinical murine and clinically available human PD-L1 antibodies limit DC migration.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P. R. China.
Cancer immunotherapies rely on CD8 cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese-bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I-deficient tumors.
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