MX2 mediates establishment of interferon response profile, regulates XAF1, and can sensitize melanoma cells to targeted therapy.

Autor: Juraleviciute M; Department of Pathology, Oslo University Hospital, Oslo, Norway.; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Nsengimana J; Faculty of Medical Sciences, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK., Newton-Bishop J; Division of Haematology and Immunology, Institute of Medical Research at St James's, University of Leeds, Leeds, UK., Hendriks GJ; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Slipicevic A; Department of Pathology, Oslo University Hospital, Oslo, Norway.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2021 Apr; Vol. 10 (8), pp. 2840-2854. Date of Electronic Publication: 2021 Mar 18.
DOI: 10.1002/cam4.3846
Abstrakt: MX2 is an interferon inducible gene that is mostly known for its antiviral activity. We have previously demonstrated that MX2 is also associated with the tumorigenesis process in melanoma. However, it remains unknown which molecular mechanisms are regulated by MX2 in response to interferon signaling in this disease. Here, we report that MX2 is necessary for the establishment of an interferon-induced transcriptional profile partially through regulation of STAT1 phosphorylation and other interferon-related downstream factors, including proapoptotic tumor suppressor XAF1. MX2 and XAF1 expression tightly correlate in both cultured melanoma cell lines and in patient-derived primary and metastatic tumors, where they also are significantly related with survival. MX2 mediates IFN growth-inhibitory signals in both XAF1 dependent and independent ways and in a cell type and context-dependent manner. Higher MX2 expression renders melanoma cells more sensitive to targeted therapy drugs such as vemurafenib and trametinib; however, this effect is XAF1 independent. In summary, we uncovered a new mechanism in the complex regulation of interferon signaling in melanoma that can influence both survival and response to therapy.
(© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje