Interplay between interferon-stimulated gene 15/ISGylation and interferon gamma signaling in breast cancer cells

Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that conjugates to its target proteins to modify them through ISGylation, but the relevance of ISG15 expression and its effects have been not completely defined. Herein, we examined the interplay between ISG15/ISGylation and the inter...

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Bibliographic Details
Published in:Cellular signalling 2019-02, Vol.54, p.91-101
Main Authors: Tecalco-Cruz, Angeles C., Cortés-González, Carlo César, Cruz-Ramos, Eduardo, Ramírez Jarquín, Josué O., Romero-Mandujano, Aline Kay, Sosa-Garrocho, Marcela
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - metabolism
Breast cancer
Breast Neoplasms - metabolism
Carcinoma - metabolism
Cytokines - metabolism
Cytoskeleton
Cytoskeleton - metabolism
Female
Humans
Interferon gamma
Interferon-gamma - metabolism
ISG15
ISGylation
MCF-7 Cells
ras GTPase-Activating Proteins - metabolism
Tumor Microenvironment
Ubiquitins - metabolism
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Summary:Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that conjugates to its target proteins to modify them through ISGylation, but the relevance of ISG15 expression and its effects have been not completely defined. Herein, we examined the interplay between ISG15/ISGylation and the interferon-gamma (IFN-γ) signaling pathway in mammary tumors and compared it with that in normal mammary tissues. Our results indicated that mammary tumors had higher levels of ISG15 mRNA and ISG15 protein than the adjacent normal mammary tissue. Furthermore, the expression of IFN-γ signaling components was altered in breast cancer. Interestingly, IFN-γ treatment induced morphological changes in MCF-7 and MDA-MB-231 breast cancer cell lines due to cytoskeletal reorganization. This cellular process seems to be related to the increase in ISGylation of cytoplasmic IQ Motif Containing GTPase Activating Protein 1 (IQGAP1). Interactome analysis also indicated that IFN-γ signaling and the ISGylation system are associated with several proteins implicated in cytoskeletal remodeling, including IQGAP1. Thus, ISG15 may present a potential biomarker for breast cancer, and IFN-γ signaling and protein ISGylation may participate in the regulation of the cytoskeleton in breast cancer cells. •ISG15 can be a biomarker for breast cancer.•The expression of IFN-γ signaling components is altered in breast cancer.•IFN-γ signaling regulates the cytoskeleton of breast cancer cells.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2018.11.021