Deyin Guo group found the anti-virus innate immune function and its mechanism of the tumor suppressor PTEN
Source：Deyin Guo
2016-03-15
Dr. Deyin Guo and colleagues, College of Life Sciences & School of Medicine, Wuhan University, reveal that the tumor suppressor PTEN also plays a pivotal role in innate immunity and antiviral responses. The results were published in the recent issue of Nature Immunology of March, 2016. In the same issue, Drs. B. Champion, K Fischer, and L. Seymour, University of Oxford, wrote in the “News and Views” to specifically comment on the discovery and its clinical relevance. The paper was also first available in the Advance Online Publication of Nature Immunology on January 21, 2015.
Innate immunity represents the first-line of host defense against pathogen infection. It is also involved in activation and regulation of adaptive immune responses. In past 20 years, type I interferon response, one of the main themes in innate immunity, has been extensively studied, leading to a series of breakthrough findings in this field. However, the molecular mechanisms on type I interferon production and antiviral immune responses are still poorly understood.
The gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) was identified as a tumor suppressor gene by several groups in 1997. The protein PTEN encoded by the gene possesses phosphatase activity with the ability to antagonize PI3K/Akt signaling pathway, thus leading to tumor suppression. Mutations or deficiency of PTEN are frequently correlated with many types of human cancers, including breast, endometrium, thyroid, leukemia, prostate, glioma, lung, liver cancers. In this study, Dr. Guo et al. found that PTEN plays an essential role in type I interferon response and antiviral immunity, and this function is not mediated through suppression of PI3K/Akt pathway but through regulation of phosphorylation/dephosphorylation and licencing of nuclear import of the IRF3, the master transcriptional factor for type I interferon responses.
The authors further revealed that PTEN-deficient cells are impaired in interferon production and become more sensitive to virus infection. This finding can partly explain why many cancer cell types are more efficiently infected by oncolytic viruses than the healthy cells, and may pave the way to develop more effective and specific strategy in oncolytic tumor therapy. In summary, the current study not only reveals a new function of PTEN and the novel mechanisms in the regulation of type I interferon response and antiviral immunity, it also have clinical relevance for improving oncolytic tumor therapy.
Innate immunity represents the first-line of host defense against pathogen infection. It is also involved in activation and regulation of adaptive immune responses. In past 20 years, type I interferon response, one of the main themes in innate immunity, has been extensively studied, leading to a series of breakthrough findings in this field. However, the molecular mechanisms on type I interferon production and antiviral immune responses are still poorly understood.
The gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) was identified as a tumor suppressor gene by several groups in 1997. The protein PTEN encoded by the gene possesses phosphatase activity with the ability to antagonize PI3K/Akt signaling pathway, thus leading to tumor suppression. Mutations or deficiency of PTEN are frequently correlated with many types of human cancers, including breast, endometrium, thyroid, leukemia, prostate, glioma, lung, liver cancers. In this study, Dr. Guo et al. found that PTEN plays an essential role in type I interferon response and antiviral immunity, and this function is not mediated through suppression of PI3K/Akt pathway but through regulation of phosphorylation/dephosphorylation and licencing of nuclear import of the IRF3, the master transcriptional factor for type I interferon responses.
The authors further revealed that PTEN-deficient cells are impaired in interferon production and become more sensitive to virus infection. This finding can partly explain why many cancer cell types are more efficiently infected by oncolytic viruses than the healthy cells, and may pave the way to develop more effective and specific strategy in oncolytic tumor therapy. In summary, the current study not only reveals a new function of PTEN and the novel mechanisms in the regulation of type I interferon response and antiviral immunity, it also have clinical relevance for improving oncolytic tumor therapy.
