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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.

Author information

1
IRIBHM, Campus Erasme, ULB Bâtiment C, 808 route de Lennik, 1070 Bruxelles, Belgium.
2
Stem cell and Cancer group, ULB Campus Erasme, 1070 Brussels, Belgium.
3
Center for Microscopy and Molecular Imaging ULB, 12 rue des professeurs Jeener et Brachet, 6041 Charleroi, Belgium.
4
Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
5
International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic.
6
IRIBHM, Campus Erasme, ULB Bâtiment C, 808 route de Lennik, 1070 Bruxelles, Belgium cerneux@ulb.ac.be.

Abstract

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.

KEYWORDS:

Breast cancer cell; Cell migration; Phosphoinositide; SHIP2

PMID:
30012834
DOI:
10.1242/jcs.216408

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