Pro-oncogenic properties of mutant p53 were investigated with the aid of migration assays, adhesion assays, and soft agar growth assays using cells stably expressing gain-of-function p53 mutants. To determine cell migration, "wound-healing" (scratch) assays and haptotactic (chamber) assays were used. H1299 cells expressing mutant p53 were found to migrate more rapidly than cells transfected with empty vector alone. Results from both types of migration assay were broadly similar. Migratory ability differed for different p53 mutants, suggesting allele-specific effects. Cells expressing p53 mutants also showed enhanced adhesion to extracellular matrix compare to controls. Furthermore, stable transfection of mutant p53-H179L into NIH3T3 fibroblasts was sufficient to allow anchorage-independent growth in soft agar.
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http://dx.doi.org/10.1007/978-1-62703-236-0_11 | DOI Listing |
Histopathology
January 2025
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Aims: Classification and risk stratification of endometrial carcinoma (EC) has transitioned from histopathological features to molecular classification, e.g. the ProMisE classifier, identifying four prognostic subtypes: POLE mutant (POLEmut) with almost no recurrence or disease-specific death events, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP), with intermediate outcome and p53 abnormal (p53abn) with poor outcomes.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Discovery Biology, PMV Pharmaceuticals, Inc., 400 Alexander Park Drive, Suite 301, Princeton, New Jersey 08540, United States.
p53 is a potent transcription factor that is crucial in regulating cellular responses to stress. Mutations in the gene are found in >50% of human cancers, predominantly occurring in the DNA-binding domain (amino acids 94-292). The Y220C mutation accounts for 1.
View Article and Find Full Text PDFCell Rep Med
January 2025
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address:
The analysis of cell-free tumor DNA (ctDNA) and proteins in the blood of patients with cancer potentiates a new generation of non-invasive diagnostic approaches. However, confident detection of tumor-originating markers is challenging, especially in the context of brain tumors, where these analytes in plasma are extremely scarce. Here, we apply a sensitive single-molecule technology to profile multiple histone modifications on individual nucleosomes from the plasma of patients with diffuse midline glioma (DMG).
View Article and Find Full Text PDFMol Divers
January 2025
School of Sciences, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, People's Republic of China.
The p53 protein is regarded as the "Guardian of the Genome," but its mutation is tumor progression and present in more than half of malignant tumors. The pro-metastatic property of mutant p53 makes a strong argument for targeting mutant p53 with new therapeutic strategies. However, mutant p53 was considered as a challenging target for drug discovery due to the lack of small molecular binding pockets.
View Article and Find Full Text PDFMolecules
January 2025
Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
MDM2 and MDM4 are major negative regulators of tumor suppressor p53. Beyond regulating p53, MDM2 possesses p53-independent activity in promoting cell cycle progression and tumorigenesis via its RING domain ubiquitin E3 ligase activity. MDM2 and MDM4 form heterodimer polyubiquitin E3 ligases via their RING domain interaction.
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