The good and the bad faces of STAT1 in solid tumours

Abstract

Signal transducer and activator of transcription (STAT) 1 is part of the Janus kinase (JAK)/STAT signalling cascade and is best known for its essential role in mediating responses to all types of interferons (IFN). STAT1 regulates a variety of cellular processes, such as antimicrobial activities, cell proliferation and cell death. It exerts important immune modulatory activities both in the innate and the adaptive arm of the immune system. Based on studies in mice and data from human patients, STAT1 is generally considered a tumour suppressor but there is growing evidence that it can also act as a tumour promoter. This review aims at contrasting the two faces of STAT1 in tumourigenesis and providing an overview on the current knowledge of the underlying mechanisms or pathways.

Transcriptional-mediated effects of radiation on the expression of immune susceptibility markers in melanoma

“…At the same time, we observed diminished activation of STAT3, which prior studies have shown to suppress STAT1 activity along with inflammatory immune pathways [27–28]. Although these results do not provide direct evidence that STAT1 mediates the RT-induced immunomodulation observed, they support prior studies that have implicated the STAT1 signaling pathway in regulating expression of MHC-I, PD-L1, and various immune-stimulatory cytokines [29–30]. Given that the STAT signaling pathway is activated directly and indirectly (via IFN signaling) by RT, we hypothesize that STAT1 plays a key role in regulating RT-induced immunomodulation and we are moving ahead with further studies to test this.…”

Dichotomal functions of phosphorylated and unphosphorylated STAT1 in hepatocellular carcinoma

“…As the active form of STAT1, p-STAT1 has been widely recognized as the functional form in inhibiting tumor growth through inducing cell apoptosis and regulating cell cycle [8, 21]. Because p-STAT1 is absent in HCC cells, IFN-α was employed to activate STAT1 phosphorylation.…”

“…They elicit antitumor effects by directly controlling tumor cells or indirectly by regulating immune response [6]. On the contrary, the pro-tumorigenic effect of IFNs, which may help the tumor escape the recognition of the immune system through “immunoediting,” has also been reported [7, 8]. However, which side wins the tussle appears to be dependent on the context of tumor type, microenvironmental factors, and signaling intensity [7].…”

“…On the other hand, STAT1 can also be a tumor promoter as it can promote tumor cell growth, therapy resistance, and immune suppression [16, 17]. In addition, expression of STAT1 has been found to correlate with both good and poor prognosis in different types of cancers [8]. Although STAT1 was reported to be a potential suppressor in HCC [18], the findings are based on limited numbers of patients and a modest effect on HCC cell growth.…”

Increased STAT1 Expression in High Grade Serous Ovarian Cancer Is Associated With a Better Outcome

“…STAT1 is also involved in tumor immunoediting by increasing the cytotoxicity of natural killer cells, cytotoxic T lymphocytes, promoting antigenpresenting function of dendritic cells and influences the expression of surface receptors on tumor cells, facilitating their elimination by the immune system. 19 One prominent feature in patients who respond to immunomodulatory therapies is the high number of intratumoral preexisting CD8 + T lymphocytes, 20 which emphasizes the need for complementary strategies to activate antitumor cytotoxic immune response.…”