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J Cell Sci. 2018 Aug 16;131(16). pii: jcs216408. doi: 10.1242/jcs.216408.

Inhibition of SHIP2 activity inhibits cell migration and could prevent metastasis in breast cancer cells.

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IRIBHM, Campus Erasme, ULB Bâtiment C, 808 route de Lennik, 1070 Bruxelles, Belgium.
Stem cell and Cancer group, ULB Campus Erasme, 1070 Brussels, Belgium.
Center for Microscopy and Molecular Imaging ULB, 12 rue des professeurs Jeener et Brachet, 6041 Charleroi, Belgium.
Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic.
IRIBHM, Campus Erasme, ULB Bâtiment C, 808 route de Lennik, 1070 Bruxelles, Belgium


Metastasis of breast cancer cells to distant organs is responsible for ∼50% of breast cancer-related deaths in women worldwide. SHIP2 (also known as INPPL1) is a phosphoinositide 5-phosphatase for phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2]. Here we show, through depletion of SHIP2 in triple negative MDA-MB-231 cells and the use of SHIP2 inhibitors, that cell migration appears to be positively controlled by SHIP2. The effect of SHIP2 on migration, as observed in MDA-MB-231 cells, appears to be mediated by PI(3,4)P2. Adhesion on fibronectin is always increased in SHIP2-depleted cells. Apoptosis measured in MDA-MB-231 cells is also increased in SHIP2-depleted cells as compared to control cells. In xenograft mice, SHIP2-depleted MDA-MB-231 cells form significantly smaller tumors than those formed by control cells and less metastasis is detected in lung sections. Our data reveal a general role for SHIP2 in the control of cell migration in breast cancer cells and a second messenger role for PI(3,4)P2 in the migration mechanism. In MDA-MB-231 cells, SHIP2 has a function in apoptosis in cells incubated in vitro and in mouse tumor-derived cells, which could account for its role on tumor growth determined in vivo.


Breast cancer cell; Cell migration; Phosphoinositide; SHIP2


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