title: STC-1 expression is upregulated through an Akt/NF-κB-dependent pathway in triple-negative breast cancer cells.
abstract: Stanniocalcin-1 (STC-1) is a secreted glycoprotein and its expression is strongly correlated with cancer development. However, regulatory mechanism of STC-1 expression in breast cancer cells is not clear. In the present study, we investigated whether STC-1 acts as a prognostic factor in TNBC patients and the regulation of STC-1 expression in breast cancer cells. Basal levels of STC-1 were significantly higher in TNBC cells than in non-TNBC cells. Induction of STC-1 expression was also associated with poor relapse-free survival of TNBC patients. In addition, we verified the correlation between the invasiveness of TNBC cells and the STC-1 expression. We found that recombinant human STC-1 treatment increased the invasiveness of TNBC cells. In contrast, STC-1-induced cell invasiveness was completely inhibited by anti-STC-1 monoclonal antibody treatment. We found that the basal levels of STC-1 expression in TNBC cells were decreased by treatment with LY294002 or Bay11-7085, but not SB203580. In contrast, transcript levels of STC-1 and protein secretion were increased by constitutively active Akt (CA-Akt) or NF-κB overexpression in TNBC cells. Finally, we observed that phosphorylation of NF-κB was significantly increased by CA-Akt overexpression in TNBC cells. Taken together, elevated STC-1 expression is associated with poor clinical outcome in TNBC patients, and STC-1 is directly involved in the invasiveness of TNBC cells. STC-1 expression is upregulated through a PI-3K/Akt/NF-κB‑dependent signaling pathway in TNBC cells.
authors.affiliation: Department of Surgery, Samsung Medical Center, Seoul 06351, Republic of Korea.
authors.forename: Myeongjin
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Surgery, Samsung Medical Center, Seoul 06351, Republic of Korea.
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Surgery, Samsung Medical Center, Seoul 06351, Republic of Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Department of Surgery, Samsung Medical Center, Seoul 06351, Republic of Korea.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Seoul 06351, Republic of Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D006023:Glycoproteins; D016328:NF-kappa B; C051795:teleocalcin; D051057:Proto-Oncogene Proteins c-akt