Premium
Lipid phosphatases SKIP and SHIP 2 regulate fibronectin‐dependent cell migration in glioblastoma
Author(s) -
Ramos Ana Raquel,
Ghosh Somadri,
Dedobbeleer Matthias,
Robe Pierre A.,
Rogister Bernard,
Erneux Christophe
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14769
Subject(s) - lamellipodium , cell migration , fibronectin , downregulation and upregulation , pten , microbiology and biotechnology , motility , cell , colocalization , phosphatase , cell culture , chemistry , biology , phosphorylation , signal transduction , pi3k/akt/mtor pathway , biochemistry , extracellular matrix , genetics , gene
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.