Fascin1 suppresses RIG-I-like receptor signaling and interferon-β production by associating with IκB kinase ϵ (IKKϵ) in colon cancer

The Journal of Biological Chemistry
Tomio MatsumuraShin-Ichi Miyagawa

Abstract

Fascin1 is an actin-bundling protein involved in cancer cell migration and has recently been shown also to have roles in virus-mediated immune cell responses. Because viral infection has been shown to activate immune cells and to induce interferon-β expression in human cancer cells, we evaluated the effects of fascin1 on virus-dependent signaling via the membrane- and actin-associated protein RIG-I (retinoic acid-inducible gene I) in colon cancer cells. We knocked down fascin1 expression with shRNA retrovirally transduced into a DLD-1 colon cancer and L929 fibroblast-like cell lines and used luciferase reporter assays and co-immunoprecipitation to identify fascin1 targets. We found that intracellular poly(I·C) transfection to mimic viral infection enhances the RIG-I/MDA5 (melanoma differentiation-associated gene 5)-mediated dimerization of interferon regulatory factor 3 (IRF-3). The transfection also significantly increased the expression levels of IRF-7, interferon-β, and interferon-inducible cytokine IP-10 in fascin1-deleted cells compared with controls while significantly suppressing cell growth, migration, and invasion. We also found that fascin1 constitutively interacts with IκB kinase ϵ (IKKϵ) in the RIG-I signaling pathw...Continue Reading

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Citations

Apr 30, 2019·Journal of Cellular Biochemistry·Ying ChenQing Yang
Mar 19, 2020·International Journal of Molecular Sciences·Begoña Alburquerque-GonzálezPablo Conesa-Zamora
Jul 19, 2020·BMC Cancer·Fuyan HuXiaoping Liu

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