Han Jeonghun, Jeon Myeongjin, Shin Incheol, Kim Sangmin
Department of Surgery, Samsung Medical Center, Seoul, Republic of Korea.
Department of Life Science, Hanyang University, Seoul, Republic of Korea.
Oncol Rep. 2016 Sep;36(3):1764-71. doi: 10.3892/or.2016.4977. Epub 2016 Jul 26.
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.
鲽源钙素-1（STC-1）是一种分泌型糖蛋白，在多种人类恶性肿瘤中高表达。然而，STC-1在乳腺癌细胞中的作用尚未完全阐明。在此，我们研究了STC-1是否作为三阴性乳腺癌（TNBC）患者的预后因素，并探讨了其在乳腺癌细胞中的细胞机制。STC-1的表达水平与基底型乳腺癌患者的无复发生存期和总生存期直接相关。STC-1水平高的乳腺癌患者预后较差。此外，我们的结果显示，TNBC中STC-1的表达水平明显高于非TNBC细胞。重组人STC-1处理后，TNBC细胞的侵袭性也显著增加。相反，在Hs578T和MDA-MB-231 TNBC细胞中，STC-1 siRNA过表达使侵袭细胞数量完全减少。我们的结果显示，在Hs578T和MDA-MB-231 TNBC细胞中，STC-1处理后c-Jun氨基末端蛋白激酶（JNK）和c-Jun的磷酸化增加，但ERK和p38 MAPK的磷酸化未增加。此外，STC-1处理使一种侵袭相关基因MMP-9的表达增加。在Hs578T细胞中，SP600125（一种JNK抑制剂）抑制了STC-1诱导的MMP-9表达。SP600125也抑制了STC-1诱导的细胞侵袭性。综上所述，我们证明异常的STC-1表达与预后不良相关，并通过JNK/c-Jun依赖性信号通路刺激TNBC细胞的侵袭性。
