The knocking down of the oncoprotein Golgi phosphoprotein 3 in T98G cells of glioblastoma multiforme disrupts cell migration by affecting focal adhesion dynamics in a focal adhesion kinase-dependent manner

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dc.contributor.authorArriagada, Cecilia
dc.contributor.authorLuchsinger, Charlotte
dc.contributor.authorGonzález, Alexis E.
dc.contributor.authorSchwenke, Tomás
dc.contributor.authorArriagada, Gloria
dc.contributor.authorFolch, Hugo
dc.contributor.authorEhrenfeld, Pamela
dc.contributor.authorBurgos, Patricia V.
dc.contributor.authorMardones, Gonzalo A.
dc.date.accessioned2023-07-27T16:48:47Z
dc.date.available2023-07-27T16:48:47Z
dc.date.issued2019-02
dc.descriptionIndexación Scopuses
dc.description.abstractGolgi phosphoprotein 3 (GOLPH3) is a conserved protein of the Golgi apparatus that in humans has been implicated in tumorigenesis. However, the precise function of GOLPH3 in malignant transformation is still unknown. Nevertheless, clinicopathological data shows that in more than a dozen kinds of cancer, including gliomas, GOLPH3 could be found overexpressed, which correlates with poor prognosis. Experimental data shows that overexpression of GOLPH3 leads to transformation of primary cells and to tumor growth enhancement. Conversely, the knocking down of GOLPH3 in GOLPH3-overexpressing tumor cells reduces tumorigenic features, such as cell proliferation and cell migration and invasion. The cumulative evidence indicate that GOLPH3 is an oncoprotein that promotes tumorigenicity by a mechanism that impact at different levels in different types of cells, including the sorting of Golgi glycosyltransferases, signaling pathways, and the actin cytoskeleton. How GOLPH3 connects mechanistically these processes has not been determined yet. Further studies are important to have a more complete understanding of the role of GOLPH3 as oncoprotein. Given the genetic diversity in cancer, a still outstanding aspect is how in this inherent heterogeneity GOLPH3 could possibly exert its oncogenic function. We have aimed to evaluate the contribution of GOLPH3 overexpression in the malignant phenotype of different types of tumor cells. Here, we analyzed the effect on cell migration that resulted from stable, RNAi-mediated knocking down of GOLPH3 in T98G cells of glioblastoma multiforme, a human glioma cell line with unique features. We found that the reduction of GOLPH3 levels produced dramatic changes in cell morphology, involving rearrangements of the actin cytoskeleton and reduction in the number and dynamics of focal adhesions. These effects correlated with decreased cell migration and invasion due to affected persistence and directionality of cell motility. Moreover, the knocking down of GOLPH3 also caused a reduction in autoactivation of focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase that regulates focal adhesions. Our data support a model in which GOLPH3 in T98G cells promotes cell migration by stimulating the activity of FAK.es
dc.identifier.citationPLoS ONE Volume 14, Issue 2 February 2019 Article number e0212321es
dc.identifier.doi10.1371/journal.pone.0212321en
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/52064
dc.language.isoenes
dc.publisherPLoS ONEes
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.esen
dc.subjectBrain Neoplasmses
dc.subjectCell Line, Tumores
dc.subjectCell Movementes
dc.subjectCell Proliferationes
dc.subjectFocal Adhesion Protein-Tyrosine Kinaseses
dc.subjectFocal Adhesionses
dc.subjectGlioblastomaes
dc.subjectHumanses
dc.subjectMembrane Proteinses
dc.subjectPhosphorylationes
dc.subjectRNA Interferencees
dc.subjectRNA, Small Interferinges
dc.titleThe knocking down of the oncoprotein Golgi phosphoprotein 3 in T98G cells of glioblastoma multiforme disrupts cell migration by affecting focal adhesion dynamics in a focal adhesion kinase-dependent manneres
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