IFNγ induces JAK1/STAT1/p65 NFκB-dependent interleukin-8 expression in ovarian cancer cells, resulting in their increased migration

被引：12

作者：

Padmanabhan, Sveta ^{[1
]}

Gaire, Bijaya ^{[1
]}

Zou, Yue ^{[1
]}

Uddin, Mohammad M. ^{[1
]}

DeLeon, Daniel ^{[1
]}

Vancurova, Ivana ^{[1
]}

机构：

[1] St Johns Univ, Dept Biol Sci, Queens, NY 11439 USA

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2021年 / 141卷

基金：

美国国家卫生研究院;

关键词：

Interferon-gamma; Interleukin-8; JAK1; STAT1; p65NF kappa B; Ovarian cancer; Cell invasion; REDUCED CLINICAL BENEFIT; INTERFERON-GAMMA; SERUM INTERLEUKIN-8; 1ST-LINE TREATMENT; IMMUNE-RESPONSES; RANDOMIZED-TRIAL; REGULATORY T; ACETYLATION; PROGRESSION; MELANOMA;

D O I：

10.1016/j.biocel.2021.106093

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interferon-gamma (IFN gamma) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFN gamma has been used in cancer treatment. However, IFN gamma also has tumor-promoting functions that are less well understood. Here, we show that IFN gamma induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFN gamma-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NF kappa B, and is associated with an increased occupancy of K314/315 acetylated p65 NF kappa B and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody reduces IFN gamma-induced migration of OC cells, and their invasion ability in 3D spheroids. Together, these findings identify IL-8 as a novel target induced by IFN gamma/JAK1/STAT1/ p65 NF kappa B signaling, and indicate that the IFN gamma-induced IL-8 contributes to IFN gamma pro-tumorigenic effects in ovarian cancer cells.

引用

页数：10