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Investigating the Regulation of alternative splicing by extracellular matrix stiffness and cell density

dc.contributor.advisorDr. Kai Erdmann
dc.date.accessioned2025-09-30T07:42:57Z
dc.date.available2025-09-30T07:42:57Z
dc.descriptionECM stiffness was found to modulate AS patterns of key cytoskeletal and signalling genes, while high cell density reduced PTBP1’s nuclear localization, altering its splicing activity. A notable discovery is the regulation of PTBP1 subcellular localization by cell density, which influences the alternative splicing of NUMB. Specifically, we show that the inclusion of exon 9 (+E9) in NUMB generates an isoform that promotes proliferation, enabling cells to override contact inhibition of proliferation (CIP) to a certain extent. Conversely, the exclusion of exon 9 (ΔE9) produces an isoform that enforces CIP,
dc.description.abstractCells perceive and respond to mechanical stimuli in their environment through a process known as mechanotransduction, which involves converting physical cues into biological signals. Recently, it has become clear that mechanical forces play an important role in cancer initiation and progression. However, our understanding of how these mechanical signals are translated into cellular biochemical changes remains incomplete. While mechanical cues such as extracellular matrix (ECM) stiffness and cell density are increasingly recognized as key regulators of cellular behaviour, their influence on post-transcriptional processes like alternative splicing remains poorly understood. This thesis explores the mechanosensitive regulation of alternative splicing, focusing on the splicing regulator PTBP1 and its downstream targets, particularly NUMB, in mediating cellular responses to mechanical cues.
dc.identifier732
dc.identifier.urihttps://dspace.academy.edu.ly/handle/123456789/1777
dc.subjectcell density
dc.titleInvestigating the Regulation of alternative splicing by extracellular matrix stiffness and cell density
dspace.entity.typeProject
project.endDate2024
project.funder.nameمختبرات طبية
project.investigatorأحمد مختار علي سالم
project.startDate2023
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