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Analysis of Munc18c and Syntaxin4 Function During Tumour Cell Invasion

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Title: Analysis of Munc18c and Syntaxin4 Function During Tumour Cell Invasion
Author: Martynowicz, David
Department: Department of Molecular and Cellular Biology
Program: Molecular and Cellular Biology
Advisor: Coppolino, Marc
Abstract: Tumour cell invasion through the ECM (extracellular matrix) involves the precise localization of proteins required for ECM proteolysis and cell migration. Membrane trafficking events, mediated by SNAREs (Soluble NSF Attachment Protein Receptors), have been implicated in these cellular processes. Previous studies on SNAREs indicate that Syntaxin4 is involved in the formation of invadopodia (specialized degradative structures formed during tumour cell invasion) in MDA-MB-231 cells; however, it remains unclear how Syntaxin4 function is regulated during tumour cell invasion. Munc18c is a known regulator of Syntaxin4 activity, and a potential role for Munc18c in invadopodium-based ECM degradation and cell migration has been identified. Here, biochemical and microscopic analyses revealed an association between Munc18c and Syntaxin4. Munc18c knockdown perturbed invadopodium formation and cell migration. Expression of a truncated form of Syntaxin4 designed to perturb Syntaxin4-Munc18c interactions had similar effects. These results suggest Munc18c facilitates Syntaxin4 function during tumour cell invasion.
Date: 2015-12
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