11 research outputs found
Role of Hodgkin and Reed-Sternberg Cell-Derived Lymphotoxin-Alpha in T Cell Recruitment into the Microenvironment of Hodgkin Lymphoma Lesions
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A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.
c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables METN375S to interact with HER2 in a ligand-independent fashion. The resultant METN375S/HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis. Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing METN375S. These results establish METN375S as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies
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A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.
c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables METN375S to interact with HER2 in a ligand-independent fashion. The resultant METN375S/HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis. Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing METN375S. These results establish METN375S as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies
Protein Lipidation by Palmitoylation and Myristoylation in Cancer
10.3389/fcell.2021.673647FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY9complete
Dysregulation of the Ubiquitin Proteasome System in Human Malignancies: A Window for Therapeutic Intervention
10.3390/cancers13071513CANCERS13
Fatty Acid Synthase: An Emerging Target in Cancer
10.3390/molecules25173935Molecules25173935-393
Leucine-Rich ?-2-Glycoprotein 1 Suppresses Endothelial Cell Activation Through ADAM10-Mediated Shedding of TNF-? Receptor
10.3389/fcell.2021.706143Frontiers in Cell and Developmental Biology970614
The fetal mouse metatarsal bone explant as a model of angiogenesis.
The mouse fetal metatarsal provides a unique tool for studying angiogenesis. In comparison with other commonly used in vitro or ex vivo angiogenesis assays, vessel outgrowth from mouse fetal metatarsals is more representative of sprouting angiogensis in vivo. It allows the analysis of blood vessel growth, and the mechanisms underpinning this process, in a multicellular microenvironment that drives the formation of a robust and complex vascular network in the absence of exogenous growth factors. By labeling different constituents of the vascular structure, it is possible to perform 3D rendering of the spatial interplay between different cellular components and to carry out quantitative analysis of vessel outgrowth. High-resolution imaging permits the visualization of fine structural and cellular details. As the assay involves the use of fetal tissues, it is possible to follow new blood vessel formation in genetically modified mice that are perinatally lethal. The entire process takes 9–13 d. A detailed description of how to set up and perform the assay is described here.NMRC (Natl Medical Research Council, S’pore)Accepted versio