1. IFNγ induces JAK1/STAT1/p65 NFκB-dependent interleukin-8 expression in ovarian cancer cells, resulting in their increased migration.
- Author
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Padmanabhan S, Gaire B, Zou Y, Uddin MM, DeLeon D, and Vancurova I
- Subjects
- Humans, Female, Cell Line, Tumor, Signal Transduction drug effects, Gene Expression Regulation, Neoplastic drug effects, STAT1 Transcription Factor metabolism, STAT1 Transcription Factor genetics, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Ovarian Neoplasms genetics, Interleukin-8 metabolism, Interleukin-8 genetics, Interferon-gamma metabolism, Interferon-gamma pharmacology, Janus Kinase 1 metabolism, Janus Kinase 1 genetics, Transcription Factor RelA metabolism, Transcription Factor RelA genetics, Cell Movement drug effects
- Abstract
Interferon-γ (IFNγ) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFNγ has been used in cancer treatment. However, IFNγ also has tumor-promoting functions that are less well understood. Here, we show that IFNγ induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFNγ-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NFκB, and is associated with an increased occupancy of K314/315 acetylated p65 NFκB and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody reduces IFNγ-induced migration of OC cells, and their invasion ability in 3D spheroids. Together, these findings identify IL-8 as a novel target induced by IFNγ/JAK1/STAT1/p65 NFκB signaling, and indicate that the IFNγ-induced IL-8 contributes to IFNγ pro-tumorigenic effects in ovarian cancer cells., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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