STC-1 expression is upregulated through an Akt/NF-κB-dependent pathway in triple-negative breast cancer cells

Jeon,Myeongjin; Han,Jeonghun; Nam,Seok  Jin; Lee,Jeong  Eon; Kim,Sangmin

doi:10.3892/or.2016.4972

STC-1 expression is upregulated through an Akt/NF-κB-dependent pathway in triple-negative breast cancer cells

Authors:
- Myeongjin Jeon
- Jeonghun Han
- Seok Jin Nam
- Jeong Eon Lee
- Sangmin Kim
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Affiliations: Department of Surgery, Samsung Medical Center, Seoul 06351, Republic of Korea
Published online on: July 25, 2016 https://doi.org/10.3892/or.2016.4972
Pages: 1717-1722

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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.

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