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Phosphatidylinositol 4-kinase IIβ negatively regulates invadopodia formation and suppresses an invasive cellular phenotype
Author(s) -
Ganiyu O. Alli-Balogun,
Christina Gewinner,
Ruth Jacobs,
János Kriston-Vizi,
Mark G. Waugh,
Shane Minogue
Publication year - 2016
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e16-08-0564
Subject(s) - invadopodia , biology , endosome , microbiology and biotechnology , phosphatidylinositol , kinase , golgi apparatus , intracellular , cancer cell , cancer , endoplasmic reticulum , genetics
The type II phosphatidylinositol 4-kinase (PI4KII) enzymes synthesize the lipid phosphatidylinositol 4-phosphate (PI(4)P), which has been detected at the Golgi complex and endosomal compartments and 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 small interfering RNA led to actin remodeling. Depletion of PI4KIIβ also induced the formation of invadopodia containing membrane type I matrix metalloproteinase (MT1-MMP). Depletion of PI4KII isoforms also differentially affected trans-Golgi network (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 colocalization of MT1-MMP with membranes containing the endosomal markers Rab5 and Rab7 but increased localization 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 are 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 synthesizes a pool of PI(4)P that maintains MT1-MMP traffic in the degradative pathway and suppresses the formation of invadopodia.

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