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Title: Expression of N-Cadherin in EBV-Positive B-Cells and its Association with De-UbiquitinaseUCH-L1
Authors: Salahud Din, Sadia
Keywords: Biological & Medical Sciences
Issue Date: 2021
Publisher: Gomal University, D.I.Khan.
Abstract: Cell adhesion and motility are critical features of normal lymphocyte function as well as lymphoid cancer progression. Despite significant progress, the exact mechanism of motility of transformed B-cells is still unclear. Although expression and function of the N-cadherin, pro-metastatic adhesion receptor, in solid tumors is well recognized, its potential role in lymphoid cancers remains mostly unknown. Our study is exclusive in demonstrating that N-cadherin is expressed in Epstein-Barr Virus-transformed human B-cells. Endogenous expression of N-cadherin is directly related to the levels of the key Epstein-Barr Virus (EBV) oncogene, Latent Membrane Protein-1 (LMP-1). Also, we have detected a correlation between LMP1 and N-cadherin not only in EBV-infected B lymphocytes but in LMP1-positive B-lymphomas as well. A functional and dynamic link between adhesion receptors and cytoskeletal rearrangement machinery is crucial for the motility of B-lymphoma cells. Ubiquitin C-terminal Hydrolase L1, De novo expression is established in several human malignancies, including B-cell lymphomas. Current research connects UCH-L1 protein in the regulation of adhesion complexes and cytoskeletal reorganization in transformed cells. We also observed in our experiments, that N-cadherin participates in adhesion and motility of EBV-transformed B-cells and that UCH-L1 is a significant element of the adhesion complexes which were associated with N-cadherin. Furthermore, N-cadherin/UCH-L1 complexes are also part of the stress induced cellular protrusions, which indicates the potential role of these complexes in cell-cell communications in B-cell lymphomas. Finally, we provide evidence that UCH-L1 de-ubiquitinating activity regulates N-cadherin modifications and proteolysis in transformed B-cells, suggesting that targeting N-cadherin/UCH-L1 complex might be helpful for EBV-associated B-lymphoma treatment.
Gov't Doc #: 24164
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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