The Cytoplasmic Region of SARAF Reduces Triple-Negative Breast Cancer Metastasis through the Regulation of Store-Operated Calcium Entry

Triple-negative breast cancer has a poor prognosis and is non-responsive to first-line therapies; hence, new therapeutic strategies are needed. Enhanced store-operated Ca2+ entry (SOCE) has been widely described as a contributing factor to tumorigenic behavior in several tumor types, particularly in breast cancer cells. SOCE-associated regulatory factor (SARAF) acts as an inhibitor of the SOCE response and, therefore, can be a potential antitumor factor. Herein, we generated a C-terminal SARAF fragment to evaluate the effect of overexpression of this peptide on the malignancy of triple-negative breast cancer cell lines. Using both in vitro and in vivo approaches, we showed that overexpression of the C-terminal SARAF fragment reduced proliferation, cell migration, and the invasion of murine and human breast cancer cells by decreasing the SOCE response. Our data suggest that regulating the activity of the SOCE response via SARAF activity might constitute the basis for further alternative therapeutic strategies for triple-negative breast cancer.

Automated summary

Triple-negative breast cancer has a poor prognosis and lacks response to traditional therapies, necessitating the development of new treatment strategies. Enhanced store-operated Ca2+ entry (SOCE) has been associated with tumorigenic behavior in breast cancer cells. In this study, we investigated the potential antitumor effects of a C-terminal SARAF fragment and found that its overexpression decreased the proliferation, migration, and invasion of breast cancer cells by reducing the SOCE response. These findings suggest that targeting the SOCE response via SARAF activity may offer alternative therapeutic options for triple-negative breast cancer.