UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Phosphatidylinositol 4-kinase IIβ negatively regulates invadopodia formation and suppresses an invasive cellular phenotype

Alli-Balogun, GO; Gewinner, CA; Jacobs, R; Kriston-Vizi, J; Waugh, MG; Minogue, S; (2016) Phosphatidylinositol 4-kinase IIβ negatively regulates invadopodia formation and suppresses an invasive cellular phenotype. Molecular Biology of the Cell , 27 (25) pp. 4033-4042. 10.1091/mbc.E16-08-0564. Green open access

[img]
Preview
Text
Minogue_Mol. Biol. Cell-2016-Alli-Balogun-4033-42.pdf

Download (2MB) | Preview

Abstract

The type II PI 4-kinases enzymes synthesise the lipid phosphatidylinositol 4-phosphate (PI(4)P) which has been detected at the Golgi complex and endosomal compartments, and which recruits clathrin adaptors. Despite common mechanistic similarities between the isoforms, the extent of their redundancy is unclear.We found that depletion of PI4KIIα and PI4KIIβ using siRNA led to actin remodelling. Depletion of PI4KIIβ also induced the formation of invadopodia containing membrane type I matrix metalloproteinase (MT1-MMP).Depletion of PI4KII isoforms also differentially affected TGN pools of PI(4)P and post-TGN traffic. PI4KIIβ depletion caused increased MT1-MMP trafficking to invasive structures at the plasma membrane and was accompanied by reduced colocalisation of MT1-MMP with membranes containing the endosomal markers Rab5 and Rab7, but increased localisation with the exocytic Rab8. Depletion of PI4KIIβ was sufficient to confer an aggressive invasive phenotype on minimally invasive HeLa and MCF-7 cell lines. Mining oncogenomic databases revealed that loss of the PI4K2B allele and underexpression of PI4KIIβ mRNA is associated with human cancers. This finding supports the cell data and suggests that PI4KIIβ may be a clinically significant suppressor of invasion. We propose that PI4KIIβ synthesises a pool of PI(4)P that maintains MT1-MMP traffic in the degradative pathway and suppresses the formation of invadopodia.

Type: Article
Title: Phosphatidylinositol 4-kinase IIβ negatively regulates invadopodia formation and suppresses an invasive cellular phenotype
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1091/mbc.E16-08-0564
Publisher version: http://dx.doi.org/10.1091/mbc.E16-08-0564
Language: English
Additional information: © 2016 Alli-Balogun et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/1530802
Downloads since deposit
65Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item