Upregulation of SHIP2 participates in the development of breast cancer via promoting Wnt/β-catenin signaling.

Abstract

PurposeSrc homology 2-containing inositol 5-phosphatase 2 (SHIP2) gene is associated with arthrosclerosis, gastric cancer and diabetes. In this study, we revealed that overexpression of SHIP2 is closely implicated with the development of breast cancer (BC).MethodsThe BC tissue and adjacent cancerous tissue were obtained from BC patients who had underwent mastectomy. BC cells with either overexpression or knockdown of SHIP2 were analyzed to determine cell proliferation, migration, invasion and apoptosis using the CCK-8 assay, colony formation assay, scratch assay, transwell assay and flow cytometry, respectively. A rat BC xenograft model was constructed to explore the role of SHIP2 on tumor growth in vivo.ResultsThe expression levels of SHIP2 in BC tissues and cells were significantly higher than those in adjacent tissues and normal breast cells, respectively. Silencing SHIP2 suppressed BC cells proliferation and promoted apoptosis. Overexpression of SHIP2 enhanced the cells migration/invasion in BC. Moreover, SHIP2 participated in the Wnt/β-catenin pathway by regulating GSK-3β and its downstream genes. β-Catenin activator LiCl could significantly eliminate the effect of si-SHIP2 on BC cells. Moreover, overexpression of SHIP2 increased tumor volume and weight in rat model, and Wnt/β-catenin pathway inhibitor ICG001 reversed the promoting effect of SHIP2 on tumorigenesis.ConclusionUpregulation of SHIP2 could increase the migration, invasion, proliferation, and decrease apoptosis in BC cells. Moreover, SHIP2 participated in the progression of BC via activating the Wnt/β-catenin pathway.