The cell surface protease-activated receptor 1 (PAR1) is overexpressed in glioblastoma multiforme (GBM). We studied the function and structure of intracellular microtubule (MT) and PAR1 in a tubulin-mediated process. We found that exposure to thrombin increased the percentage of proliferative, S, and M phases cells, affected morphology, and increased process elongation. PAR1 antagonist inversely affects these measures, increases tubulin end-binding protein 3 (EB3) mRNA expression in C6 cells, and reduces EB3 comet length, track length, and duration in neuroblastoma cells. In addition, immunofluorescence staining suggests that PAR1 is in close association with the MT α-tubulin and with coagulation cascade proteins during cell division stages. Our findings support PAR1 involvement in MT dynamics.
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http://dx.doi.org/10.1016/j.heliyon.2024.e33329 | DOI Listing |
Mol Biol Cell
December 2024
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093.
Signaling by G protein-coupled receptors (GPCRs) is regulated by temporally distinct processes including receptor desensitization, internalization, and lysosomal sorting, and are tightly controlled by post-translational modifications. While the role of phosphorylation in regulating GPCR signaling is well studied and established, the mechanisms by which other post-translational modifications, such as ubiquitination, regulate GPCR signaling are not clearly defined. We hypothesize that GPCR ubiquitination and deubiquitination is critical for proper signaling and cellular responses.
View Article and Find Full Text PDFBeijing Da Xue Xue Bao Yi Xue Ban
December 2024
Department of Pathology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
Primary hepatoid adenocarcinoma (HAC) of the uterus is a particular tumour that bears high similarity to hepatocellular carcinoma histologically, and may easily be misdiagnosed because it is rare if you don' t remember it. In this report, we describe two cases of alpha-fetoprotein (AFP)-producing HAC of the uterus. Case 1 was a 69-year-old postmenopausal woman who was presented to the hospital for a medical examination.
View Article and Find Full Text PDFOncogene
December 2024
Department of Respiratory Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. Current treatments are insufficient in improving the prognosis of lung cancer patients with comorbid idiopathic pulmonary fibrosis (IPF-LC). Senescent fibroblasts, as stromal cells in the tumor microenvironment, influence tumor progression via exosomes.
View Article and Find Full Text PDFBr J Pharmacol
December 2024
Cardiovascular Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Background And Purpose: Pharmacological intervention of thrombosis is challenging, requiring a fined tune balance between beneficial antithrombotic effect versus risk of major bleeding complications. In this investigation, we elucidated the antithrombotic capacity of the novel 90-mer RNA aptamer Apta-1 and its underlying mechanism of action.
Experimental Approach: We utilized three independent in vivo animal models to establish antithrombotic activity and bleeding risk of Apta-1.
J Biol Chem
November 2024
School of Biological Sciences, Indian Association for the Cultivation of Science, Kolkata, India. Electronic address:
The association between idiopathic venous thrombosis and occult cancer is widely recognized. However, the comprehensive understanding of how thrombin, generated during the process of thrombosis, possesses the potential to augment the malignant phenotype is still not well understood. The coagulation protease thrombin mediates its effects by cleaving protease-activated receptor 1 (PAR1), a receptor abundantly expressed on the surface of triple-negative breast cancer (TNBC) cells.
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