Purpose: The deubiquitinating enzymes (DUBs) have been linked to cancer initiation and progression. Although ubiquitin-specific protease 33 (USP33) represents a significant factor in regulating various tumor cell behaviors, its specific biological functions and precise mechanisms in esophageal squamous cell carcinoma (ESCC) progression remain unclear.
Methods: The expressions of USP33 mRNA in GEO databases, clinical ESCC samples, and USP33 protein were analyzed using bioinformatics, RT-PCR, and immunohistochemistry, respectively. Using Kaplan-Meier survival curves, the log-rank test was used to determine the cumulative survival rate. Western blotting was used to determine indicated protein expression. The cell biological functions were evaluated by cell growth assay, transwell, cell adhesion, and cell spreading assay, respectively. The interaction between USP33 and integrins was detected by immunoprecipitation, and the deubiquitination was performed by deubiquitination assay. The metastatic ability was checked by tail vein injection.
Results: A significant positive correlation was found between USP33 expression and clinical TNM stage, T classification, and poor prognosis in patients with ESCC. USP33 promoted laminin-dependent adhesion, spreading, and migration of ESCC cells but not their proliferation. Mechanistically, USP33 mediates cell migration through binding, deubiquinating, and stabilizing integrin α6. USP33 knockdown could inhibit ESCC cell migration and metastasis majorly through integrin α6.
Conclusion: This study reveals a novel mechanism of USP33 in promoting laminin-dependent ESCC cell migration and metastasis through integrin α6, suggesting that USP33 may be a promising target for treating ESCC.
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http://dx.doi.org/10.1007/s00432-024-06041-5 | DOI Listing |
J Biol Chem
December 2024
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu, 226001, China. Electronic address:
Ischemia and hypoxia caused by vascular injury intensify nerve damage. Skin precursor-derived Schwann cells have demonstrated an accelerated in vivo pre-vascularization of tissue-engineered nerves. Furthermore, extracellular vesicles from skin precursor-derived Schwann cells (SKP-SC-EVs) show the potential in aiding peripheral nerve regeneration.
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Institute of Physiology, iCBR, Faculty of Medicine, University of Coimbra, Subunit 1, polo 3, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal.
Perivascular adipose tissue (PVAT) is a dynamic tissue that affects vascular function and cardiovascular health. The connection between PVAT, the immune system, obesity, and vascular disease is complex and plays a pivotal role in the pathogenesis of vascular diseases such as atherosclerosis, hypertension, and vascular inflammation. In cardiometabolic diseases, PVAT becomes a significant source of proflammatory adipokines, leading to increased infiltration of immune cells, in cardiometabolic diseases, PVAT becomes a significant source of proinflammatory adipokines, leading to increased infiltration of immune cells, promoting vascular smooth muscle cell proliferation and migrationpromoting vascular smooth muscle cell proliferation and migration.
View Article and Find Full Text PDFCancer Cell Int
December 2024
Department of Plastic and Aesthetic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
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View Article and Find Full Text PDFAm J Pathol
December 2024
Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. Electronic address:
Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix (ECM) remodeling for maintaining homeostasis and promoting cell migration and proliferation. Pathological conditions can alter TIMP homeostasis and aggravate disease progression. The roles of TIMPs have been studied in tissue-related disorders; however, their contributions to tissue repair during corneal injury are undefined.
View Article and Find Full Text PDFLife Sci
December 2024
Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain; Instituto de Investigación en Ingeniería de Aragón (I3A), Zaragoza, Spain. Electronic address:
Aims: CAR-T cell therapy has attracted considerable attention in recent years owing to its well-known efficacy against haematopoietic malignancies. Nevertheless, this immunotherapy fails against solid tumours due to hostile conditions found in the tumour microenvironment. In this context, many relevant biochemical factors have been thoroughly studied, but crucial mechanical cues have been underestimated.
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