Hematopoietic lineage cell-specific protein 1 (HS1), a hidden player in migration, invasion, and tumor formation, is over-expressed in ovarian carcinoma cells

Abstract

Hematopoietic lineage cell-specific protein 1 (HS1), which is the hematopoietic homolog of cortactin, is an actin-binding protein and Lyn substrate. It is upregulated in several cancers and its expression level is associated with increased cell migration, metastasis, and poor prognosis. Here we investigated the expression and roles of HS1 in ovarian carcinoma cells. We analyzed the expression of HS1 in 171 ovarian cancer specimens and determined the association between HS1 expression and clinicopathological characteristics, including patient outcomes. In patients with stage II–IV disease, positive HS1 expression was associated with significantly worse overall survival than negative expression (P < 0.05). HS1 was localized in invadopodia in some ovarian cancer cells and was required for invadopodia formation. Migration and invasion of ovarian cancer cells were suppressed by down-regulation of HS1, but increased in cells that over-expressed exogenous HS1. Furthermore, ovarian cancer cells that expressed HS1 shRNA exhibited reduced tumor formation in a mouse xenograft model. Finally, we found that tyrosine phosphorylation of HS1 was essential for cell migration and invasion. These findings show that HS1 is a useful biomarker for the prognosis of patients with ovarian carcinoma and is a critical regulator of cytoskeleton remodeling involved in cell migration and invasion.