The Role of the Golgi Protein GM130 in Cell Polarity and Tumorigenesis
Dateien
Datum
Autor:innen
Herausgeber:innen
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Titel in einer weiteren Sprache
Publikationstyp
Publikationsstatus
Erschienen in
Zusammenfassung
The Golgi apparatus is linked to the establishment of cell polarity, but the mechanism that allows the organelle to control cell polarity still remains unknown. Research in the area focused primarily on signaling from the plasma membrane to understand how polarity is established, and the small GTPase Cdc42 was identified as a main regulator of this process. Interestingly Cdc42 is mainly localized at the Golgi, thus we investigated the possibility that the Golgi regulates Cdc42 activity and by this mechanism it regulates polarity. We identified a GM130–RasGRF complex as a regulator of Cdc42 at the Golgi. Silencing GM130 results in RasGRF-dependent inhibition of the Golgi pool of Cdc42, but does not affect Cdc42 at the cell surface. Therefore, this is a specific mechanism to control a spatially restricted pool of Cdc42. Furthermore, active Cdc42 at the Golgi is important to sustain asymmetric front–rear Cdc42-GTP distribution in directionally migrating cells. We propose that the Golgi delivers active Cdc42 to the leading edge of migrating cells, thereby establishing asymmetry in Cdc42 activation at the plasma membrane and promoting directional migration. Two further observations supported a possible role for GM130 in cancer. First, concurrent to Cdc42 inhibition, silencing GM130 also results in RasGRF-dependent Ras-ERK pathway activation. Second, depletion of GM130 is sufficient to induce E-cadherin downregulation, indicative of a loss in cell polarity. We found that GM130 expression is frequently lost in colorectal and breast cancer patients. Whether the loss of GM130 solely affects polarity, or whether it affects other processes relevant for tumorigenesis remains unclear. To further investigate the role of GM130 in cancer, we analyzed the effect of GM130 depletion in a panel of breast cancer cells lines looking at processes linked to tumor progression such as survival, proliferation, adhesion, migration and invasion. We show that depletion of GM130 does not drastically affect survival, proliferation and adhesion. However, GM130 depleted cells show increased cellular velocity and increased invasiveness though matrigel, therefore supporting the view that alterations of polarity contribute to tumor progression.
These findings establish a previously unrecognized role for a GM130–RasGRF–Cdc42 connection in regulating polarity and tumorigenesis.
Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
Schlagwörter
Konferenz
Rezension
Zitieren
ISO 690
BASCHIERI, Francesco, 2015. The Role of the Golgi Protein GM130 in Cell Polarity and Tumorigenesis [Dissertation]. Konstanz: University of KonstanzBibTex
@phdthesis{Baschieri2015Golgi-30811, year={2015}, title={The Role of the Golgi Protein GM130 in Cell Polarity and Tumorigenesis}, author={Baschieri, Francesco}, address={Konstanz}, school={Universität Konstanz} }
RDF
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/30811"> <dc:language>eng</dc:language> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:title>The Role of the Golgi Protein GM130 in Cell Polarity and Tumorigenesis</dcterms:title> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/30811"/> <dc:creator>Baschieri, Francesco</dc:creator> <dcterms:abstract xml:lang="eng">The Golgi apparatus is linked to the establishment of cell polarity, but the mechanism that allows the organelle to control cell polarity still remains unknown. Research in the area focused primarily on signaling from the plasma membrane to understand how polarity is established, and the small GTPase Cdc42 was identified as a main regulator of this process. Interestingly Cdc42 is mainly localized at the Golgi, thus we investigated the possibility that the Golgi regulates Cdc42 activity and by this mechanism it regulates polarity. We identified a GM130–RasGRF complex as a regulator of Cdc42 at the Golgi. Silencing GM130 results in RasGRF-dependent inhibition of the Golgi pool of Cdc42, but does not affect Cdc42 at the cell surface. Therefore, this is a specific mechanism to control a spatially restricted pool of Cdc42. Furthermore, active Cdc42 at the Golgi is important to sustain asymmetric front–rear Cdc42-GTP distribution in directionally migrating cells. We propose that the Golgi delivers active Cdc42 to the leading edge of migrating cells, thereby establishing asymmetry in Cdc42 activation at the plasma membrane and promoting directional migration. Two further observations supported a possible role for GM130 in cancer. First, concurrent to Cdc42 inhibition, silencing GM130 also results in RasGRF-dependent Ras-ERK pathway activation. Second, depletion of GM130 is sufficient to induce E-cadherin downregulation, indicative of a loss in cell polarity. We found that GM130 expression is frequently lost in colorectal and breast cancer patients. Whether the loss of GM130 solely affects polarity, or whether it affects other processes relevant for tumorigenesis remains unclear. To further investigate the role of GM130 in cancer, we analyzed the effect of GM130 depletion in a panel of breast cancer cells lines looking at processes linked to tumor progression such as survival, proliferation, adhesion, migration and invasion. We show that depletion of GM130 does not drastically affect survival, proliferation and adhesion. However, GM130 depleted cells show increased cellular velocity and increased invasiveness though matrigel, therefore supporting the view that alterations of polarity contribute to tumor progression.<br />These findings establish a previously unrecognized role for a GM130–RasGRF–Cdc42 connection in regulating polarity and tumorigenesis.</dcterms:abstract> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-04-23T09:34:08Z</dc:date> <dc:contributor>Baschieri, Francesco</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-04-23T09:34:08Z</dcterms:available> <foaf:homepage rdf:resource="http://localhost:8080/"/> <dcterms:issued>2015</dcterms:issued> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/30811/3/Baschieri_0-287758.pdf"/> <dc:rights>terms-of-use</dc:rights> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/30811/3/Baschieri_0-287758.pdf"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> </rdf:Description> </rdf:RDF>