Lipid phosphatases SKIP and SHIP 2 regulate fibronectin‐dependent cell migration in glioblastoma
Cell migration is an important process that occurs during development and has also been linked to the motility of cancer cells. Cytoskeleton reorganization takes place in the migration process leading to lamellipodia formation. Understanding the molecular underpinnings of cell migration is particula...
Saved in:
Published in | The FEBS journal Vol. 286; no. 6; pp. 1120 - 1135 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
01.03.2019
|
Online Access | Get full text |
Cover
Loading…
Summary: | Cell migration is an important process that occurs during development and has also been linked to the motility of cancer cells. Cytoskeleton reorganization takes place in the migration process leading to lamellipodia formation. Understanding the molecular underpinnings of cell migration is particularly important in studies of glioblastoma, a highly invasive and aggressive cancer type. Two members of the phosphoinositide 5‐phosphatase family,
SKIP
and
SHIP
2, have been associated with cell migration in glioblastoma; however, the precise role these enzymes play in the process—and whether they work in concert—remains unclear. Here, we compared phosphoinositide 5‐phosphatases expression in glioblastoma primary cells and cell lines and showed that
SHIP
2 and
SKIP
expression greatly varies between different cell types, while
OCRL
, another phosphoinositide 5‐phosphatase, is constitutively expressed. Upon adhesion of U‐251
MG
cells to fibronectin,
SHIP
2,
SKIP
, and
PI
(4,5)P2 colocalized in membrane ruffles. Upregulation of
PI
(4,5)P2 was observed in
SKIP
‐depleted U‐251
MG
cells compared to control cells, but only when cells were adhered to fibronectin. Both
PTEN
‐deficient (U‐251) and
PTEN
‐containing (
LN
229) glioblastoma cells showed a decrease in cell migration velocity in response to
SKIP
downregulation. Moreover, a
SHIP
2 catalytic inhibitor lowered cell migration velocity in the U‐251
MG
cell line. We conclude that integrin activation in U‐251 cells leads to colocalization of both
SKIP
and
SHIP
2 in ruffles, where they act as potential drivers of cell migration. Depending on their expression levels in glioblastoma, phosphoinositide 5‐phosphatases could cooperate and synergize in the regulation of cell migration and adhesion. |
---|---|
ISSN: | 1742-464X 1742-4658 |
DOI: | 10.1111/febs.14769 |