Downregulation of fascin induces collective cell migration in triple­negative breast cancer.

ABSTRACT

Breast cancer (BC) is one of the most common types of cancer affecting female patients. Triple­negative BC (TNBC) is an aggressive subtype. Fascin, an actin­bundling protein, serves a significant role in cancer metastasis. Fascin overexpression is associated with poor prognosis of BC. To confirm the relationship between fascin expression and BC malignancy, the present study reviewed clinical data from 100 Japanese patients with BC and performed fresh immunohistochemical fascin examination of tissue samples. Statistical analyses showed metastasis or recurrence in 11 of 100 patients and a significant association between high fascin expression and poor prognosis. The TNBC subtype was also associated with high fascin expression. However, a few cases developed poor prognosis regardless of negative or slightly positive fascin expression. The present study established fascin knockdown (FKD) MDA­MB­231, a TNBC cell line, and investigated morphological effects of fascin on TNBC cells. FKD cells exhibited cell­cell connections and bulbous nodules of various sizes on the cell surface. Conversely, non­FKD MDA­MB­231 cells exhibited loose cell­cell connections with numerous filopodia on the cell surface. Filopodia, actin­rich plasma membrane protrusions, are composed of fascin and control cell­cell interaction, migration and wound healing. Cancer metastasis is conventionally classified into two mechanisms single and collective cell migration. Fascin increases cancer metastasis by single cell migration via filopodia on the cell surface. However, the present study suggested that following FKD, TNBC cells lost filopodia and exhibited collective cell migration.