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Confined cell migration along extracellular matrix space in vivo.
Proc Natl Acad Sci U S A
January 2025
Center for Complexity and Biosystems, Department of Environmental Science and Policy, University of Milan, 20133 Milan, Italy.
Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order.
View Article and Find Full Text PDFOncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.
Proc Natl Acad Sci U S A
January 2025
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.
View Article and Find Full Text PDFIntegrin-activating protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets.
Proc Natl Acad Sci U S A
January 2025
Oncode Institute, Hubrecht Institute-Royal Netherlands Academy of Arts and Science, Utrecht 3584 CT, The Netherlands.
Matrigel/BME, a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells [T. Sato , , 262-265 (2009); T. Sato , , 1762-1772 (2011)].
View Article and Find Full Text PDFBinding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.
Proc Natl Acad Sci U S A
January 2025
Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016.
Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.
View Article and Find Full Text PDFHydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.
Proc Natl Acad Sci U S A
January 2025
Cancer Biology & Genetics Program, Sloan Kettering Institute, New York, NY 10065.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.
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