Fascin1 suppresses RIG-I-like receptor signaling and interferon-ß production by associating with IκB kinase ϵ (IKKϵ) in colon cancer.
J Biol Chem
; 293(17): 6326-6336, 2018 04 27.
Article
en En
| MEDLINE
| ID: mdl-29496994
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-ß 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-ß, 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 pathway. In summary, we have identified fascin1 as a suppressor of the RIG-I signaling pathway associating with IκB kinase ϵ in DLD-1 colon cancer cells to suppress immune responses to viral infection.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Proteínas Portadoras
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Interferón beta
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Neoplasias del Colon
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Quinasa I-kappa B
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Proteína 58 DEAD Box
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Proteínas de Microfilamentos
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Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article