Roles of Interferon Regulatory Factor 1 in Tumor Progression and Regression: Two Sides of a Coin.

Abstract

IRF1 is a transcription factor well known for its role in IFN signaling. Although IRF1 was initially identified for its involvement in inflammatory processes, there is now evidence that it provides a function in carcinogenesis as well. IRF1 has been shown to affect several important antitumor mechanisms, such as induction of apoptosis, cell cycle arrest, remodeling of tumor immune microenvironment, suppression of telomerase activity, suppression of angiogenesis and others. Nevertheless, the opposite effects of IRF1 on tumor growth have also been demonstrated. In particular, the "immune checkpoint" molecule PD-L1, which is responsible for tumor immune evasion, has IRF1 as a major transcriptional regulator. These and several other properties of IRF1, including its proposed association with response and resistance to immunotherapy and several chemotherapeutic drugs, make it a promising object for further research. Numerous mechanisms of IRF1 regulation in cancer have been identified, including genetic, epigenetic, transcriptional, post-transcriptional, and post-translational mechanisms, although their significance for tumor progression remains to be explored. This review will focus on the established tumor-suppressive and tumor-promoting functions of IRF1, as well as the molecular mechanisms of IRF1 regulation identified in various cancers.