Interplay between interferon-stimulated gene 15/ISGylation and interferon gamma signaling in breast cancer cells |
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| Institution: | 1. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico;2. Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Tlalpan, C.P. 14080 Mexico City, Mexico;3. Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico;1. Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110122, China;2. Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China;3. The 2nd Clinical Department, China Medical University, Shenyang 110122, China;1. School of Pharmacy, Anhui Medical University, Hefei 230032, China;2. Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei 230032, China;3. The Key Laboratory of major autoimmune disease, School of Pharmacy, Anhui Medical University, Hefei, Anhui Province 230032,China;4. The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Anhui Medical University, Hefei, 230032, China |
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| Abstract: | 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. |
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