title: 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.
authors.affiliation: Department of Surgery, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Surgery, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Myeongjin
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Life Science, Hanyang University, Seoul, Republic of Korea.
authors.forename: Incheol
authors.initials: I
authors.lastname: Shin
authors.affiliation: Department of Surgery, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D016133:Polymerase Chain Reaction; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; D016755:Proto-Oncogene Proteins c-jun; C051795:teleocalcin