TY  - JOUR
A1  - Arriagada, Cecilia
A1  - Luchsinger, Charlotte
A1  - González, Alexis E.
A1  - Schwenke, Tomás
A1  - Arriagada, Gloria
A1  - Folch, Hugo
A1  - Ehrenfeld, Pamela
A1  - Burgos, Patricia V.
A1  - Mardones, Gonzalo A.
T1  - 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
T2  - PLoS one
N2  - Golgi 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.
KW  - Focal adhesions
KW  - Cell migration
KW  - Fluorescence microscopy
KW  - Immunoblotting
KW  - Cell motility
KW  - Cancer cell migration
KW  - Glioblastoma multiforme
KW  - Hyperexpression techniques
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/49145
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-491456
SN  - 1932-6203
N1  - Copyright: © 2019 Arriagada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 14
IS  - (2): e0212321
SP  - 1
EP  - 29
PB  - PLoS
CY  - Lawrence, Kan.
ER  -