Elevated STC-1 augments the invasiveness of triple-negative breast cancer cells through activation of the JNK/c-Jun signaling pathway

Abstract

Stanniocalcin-1 (STC-1), a secreted glycoprotein, is highly expressed in a variety of human malignancies. However, the role of STC-1 has not been fully elucidated in breast cancer cells. Here, we investigated whether STC-1 acts as a prognostic factor in triple-negative breast cancer (TNBC) patients, and we explored the cellular mechanism in breast cancer cells. The level of STC-1 expression was directly associated with the relapse-free and overall survival of basal-type breast cancer patients. Breast cancer patients with a high level of STC-1 had poor prognosis. In addition, our results showed that the level of STC-1 expression was markedly higher in TNBC than in non-TNBC cells. Invasiveness of the TNBC cells was also significantly increased in response to recombinant human STC-1 treatment. In contrast, the invaded cell numbers were completely decreased by STC-1 siRNA overexpression in the Hs578T and MDA-MB-231 TNBC cells. Our results showed that the phosphorylation of c-Jun N-terminal protein kinase (JNK) and c-Jun was increased after STC-1 treatment but not the phosphorylation of ERK and p38 MAPKs in the Hs578T and MDA-MB-231 TNBC cells. Furthermore, expression of one invasion-related gene MMP-9, was increased by STC-1 treatment. STC-1-induced MMP-9 expression was suppressed by SP600125 (a JNK inhibitor) in the Hs578T cells. STC-1-induced cell invasiveness was also inhibited by SP600125. Taken together, we demonstrated that aberrant STC-1 expression is associated with poor prognosis and stimulates the invasiveness of TNBC cells through the JNK/c-Jun-dependent signaling pathway.